[ { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tmma9-mta38", "eprint_status": "archive", "datestamp": "2024-01-09 22:35:34", "lastmod": "2024-01-09 22:35:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Warmack-Rebeccah-A", "name": { "family": "Warmack", "given": "Rebeccah A." }, "orcid": "0000-0002-9612-0511" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase beyond the Resting State: A Structural Perspective", "ispublished": "pub", "full_text_status": "public", "keywords": "Chemistry (miscellaneous); Analytical Chemistry; Organic Chemistry; Physical and Theoretical Chemistry; Molecular Medicine; Drug Discovery; Pharmaceutical Science", "note": "
We thank Ailiena Maggiolo, Stephanie Threatt, Trixia Buscagan, Belinda Wenke, Thomas Spatzal, Jens Kaiser, and Songye Chen for the invaluable discussions. The generous support of the Beckman Institute for the Caltech CryoEM Resource Center and Molecular Observatory was essential for the performance of the structural work at Caltech discussed in this review.
\nThis research was funded by support from the Howard Hughes Medical Institute (D.C.R.) and NIH GM143836 (R.A.W.).
\nConceptualization, R.A.W. and D.C.R.; writing—original draft preparation, R.A.W. and D.C.R.; writing—review and editing, R.A.W. and D.C.R.; visualization, R.A.W. All authors have read and agreed to the published version of the manuscript.
\nData are available in original cited literature and corresponding supporting information. Additionally, all structures discussed in this review are publicly available through the Research Collaboratory for Structural Bioinformatics Protein Data Bank.
\nThe authors declare no conflict of interest.
\nPublished - 41467_2023_Article_36636.pdf
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", "abstract": "Nitrogenase catalyzes the ATP-dependent reduction of dinitrogen to ammonia during the process of biological nitrogen fixation that is essential for sustaining life. The active site FeMo-cofactor contains a [7Fe:1Mo:9S:1C] metallocluster coordinated with an R-homocitrate (HCA) molecule. Here, we establish through single particle cryoEM and chemical analysis of two forms of the Azotobacter vinelandii MoFe-protein \u2013 a high pH turnover inactivated species and a \u2206NifV variant that cannot synthesize HCA \u2013 that loss of HCA is coupled to \u03b1-subunit domain and FeMo-cofactor disordering, and formation of a histidine coordination site. We further find a population of the \u2206NifV variant complexed to an endogenous protein identified through structural and proteomic approaches as the uncharacterized protein NafT. Recognition by endogenous NafT demonstrates the physiological relevance of the HCA-compromised form, perhaps for cofactor insertion or repair. Our results point towards a dynamic active site in which HCA plays a role in enabling nitrogenase catalysis by facilitating activation of the FeMo-cofactor from a relatively stable form to a state capable of reducing dinitrogen under ambient conditions.", "date": "2023-02-25", "date_type": "published", "publication": "Nature Communications", "volume": "14", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 1091", "id_number": "CaltechAUTHORS:20230630-537337000.8", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230630-537337000.8", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "NIH", "grant_number": "GM143836-01" }, { "agency": "NSF", "grant_number": "CHE-1531940" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "Caltech Beckman Institute" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" } ] }, "doi": "10.1038/s41467-023-36636-4", "pmcid": "PMC9968304", "primary_object": { "basename": "41467_2023_36636_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_36636_MOESM3_ESM.pdf" }, "related_objects": [ { "basename": "41467_2023_36636_MOESM4_ESM.xls", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_36636_MOESM4_ESM.xls" }, { "basename": "41467_2023_36636_MOESM5_ESM.mov", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_36636_MOESM5_ESM.mov" }, { "basename": "41467_2023_36636_MOESM6_ESM.mp4", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_36636_MOESM6_ESM.mp4" }, { "basename": "41467_2023_36636_MOESM8_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_36636_MOESM8_ESM.xlsx" }, { "basename": "41467_2023_Article_36636.pdf", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_Article_36636.pdf" }, { "basename": "41467_2023_36636_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/dhhy4-y6k16/files/41467_2023_36636_MOESM1_ESM.pdf" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Warmack, Rebeccah A.; Maggiolo, Ailiena O.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r09ax-a6w50", "eprint_id": 118324, "eprint_status": "archive", "datestamp": "2023-08-22 18:34:22", "lastmod": "2023-12-21 23:32:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Threatt-Stephanie-D", "name": { "family": "Threatt", "given": "Stephanie D." }, "orcid": "0000-0002-2303-2166" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Biological nitrogen fixation in theory, practice, and reality: a perspective on the molybdenum nitrogenase system", "ispublished": "pub", "full_text_status": "public", "keywords": "Cell Biology; Genetics; Molecular Biology; Biochemistry; Structural Biology; Biophysics", "note": "\u00a9 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. \n\nWe thank Dr Rebecca Warmack, Dr Trixia Buscagan, Dr Siobhan MacArdle and Ailiena Maggiolo for discussions, and Prof William Goddard and Charles Musgrave for their invaluable advice and insights on density functional calculations on nitrogenase. This work was supported by the Howard Hughes Medical Institute.\n\nPublished - FEB2-597-45.pdf
", "abstract": "Nitrogenase is the sole enzyme responsible for the ATP-dependent conversion of atmospheric dinitrogen into the bioavailable form of ammonia (NH\u2083), making this protein essential for the maintenance of the nitrogen cycle and thus life itself. Despite the widespread use of the Haber\u2013Bosch process to industrially produce NH\u2083, biological nitrogen fixation still accounts for half of the bioavailable nitrogen on Earth. An important feature of nitrogenase is that it operates under physiological conditions, where the equilibrium strongly favours ammonia production. This biological, multielectron reduction is a complex catalytic reaction that has perplexed scientists for decades. In this review, we explore the current understanding of the molybdenum nitrogenase system based on experimental and computational research, as well as the limitations of the crystallographic, spectroscopic, and computational techniques employed. Finally, essential outstanding questions regarding the nitrogenase system will be highlighted alongside suggestions for future experimental and computational work to elucidate this essential yet elusive process.", "date": "2023-01", "date_type": "published", "publication": "FEBS Letters", "volume": "597", "number": "1", "publisher": "Wiley", "pagerange": "45-58", "id_number": "CaltechAUTHORS:20221212-796808400.40", "issn": "0014-5793", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221212-796808400.40", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1002/1873-3468.14534", "pmcid": "PMC10100503", "primary_object": { "basename": "FEB2-597-45.pdf", "url": "https://authors.library.caltech.edu/records/r09ax-a6w50/files/FEB2-597-45.pdf" }, "resource_type": "article", "pub_year": "2023", "author_list": "Threatt, Stephanie D. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tcf9s-6ab51", "eprint_id": 118086, "eprint_status": "archive", "datestamp": "2023-08-22 18:13:50", "lastmod": "2023-10-24 23:13:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "MacArdle-Siobh\u00e1n-G", "name": { "family": "MacArdle", "given": "Siobh\u00e1n G." }, "orcid": "0000-0001-7843-5977" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Solvent Deuterium Isotope Effects of Substrate Reduction by Nitrogenase from Azotobacter vinelandii", "ispublished": "pub", "full_text_status": "public", "keywords": "Colloid and Surface Chemistry; Biochemistry; General Chemistry; Catalysis", "note": "The authors thank Dr. Nathan Dalleska for guidance in GC\u2013MS methods and data analysis, Dr. Jay Winkler for FTIR quantification and analysis of ethylene isotopologues, and Dr. David Vander Velde for guidance with NMR analysis. This project benefited from the use of instrumentation made available by the Resnick Sustainability Institute's Water and Environment Lab at the California Institute of Technology. FTIR spectra were recorded in the Beckman Institute Laser Resource Center at Caltech. The authors thank Dr. Trixia Buscagan, Dr. Rebeccah Warmack, Ailiena Maggiolo, and Dr. Stephanie Threatt for nitrogenase discussions. Discussions with Prof. Ralf Thauer on unpublished proton inventory studies with methyl coenzyme M reductase and Prof. James Howard (1942\u20132022) on nitrogenase, and enzyme mechanisms generally, are gratefully acknowledged. This work was generously funded by grants from the National Institute of Health (NIH GM045162) and the Howard Hughes Medical Institute to DCR and the Parsons Graduate Fellowship to SGM. This paper was adapted from Siobh\u00e1n MacArdle's PhD thesis from the California Institute of Technology.", "abstract": "The mechanism of nitrogenase, the enzyme responsible for biological nitrogen fixation, has been of great interest for understanding the catalytic strategy utilized to reduce dinitrogen to ammonia under ambient temperatures and pressures. The reduction mechanism of nitrogenase is generally envisioned as involving multiple cycles of electron and proton transfers, with the known substrates requiring at least two cycles. Solvent kinetic isotope effect experiments, in which changes of reaction rates or product distribution are measured upon enrichment of solvent with heavy atom isotopes, have been valuable for deciphering the mechanism of complex enzymatic reactions involving proton or hydrogen transfer. We report the distribution of ethylene, dihydrogen, and methane isotopologue products measured from nitrogenase-catalyzed reductions of acetylene, protons, and cyanide, respectively, performed in varying levels of deuterium enrichment of the solvent. As has been noted previously, the total rate of product formation by nitrogenase is largely insensitive to the presence of D\u2082O in the solvent. Nevertheless, the incorporation of H/D into products can be measured for these substrates that reflect solvent isotope effects on hydrogen atom transfers that are faster than the overall rate-determining step for nitrogenase. From these data, a minimal isotope effect is observed for acetylene reduction (1.4 \u00b1 0.05), while the isotope effects for hydrogen and methane evolution are significantly higher at 4.2 \u00b1 0.1 and 4.4 \u00b1 0.1, respectively. These results indicate that there are pronounced differences in the sensitivity to isotopic substitution of the hydrogen atom transfer steps associated with the reduction of these substrates by nitrogenase.", "date": "2022-11-23", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "144", "number": "46", "publisher": "American Chemical Society", "pagerange": "21125-21135", "id_number": "CaltechAUTHORS:20221128-494241100.48", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221128-494241100.48", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" } ] }, "doi": "10.1021/jacs.2c07574", "resource_type": "article", "pub_year": "2022", "author_list": "MacArdle, Siobh\u00e1n G. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/nhrcf-q4974", "eprint_id": 117279, "eprint_status": "archive", "datestamp": "2023-08-22 17:50:11", "lastmod": "2023-10-24 22:28:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Miller-Ryan-D", "name": { "family": "Miller", "given": "Ryan D." }, "orcid": "0000-0002-0723-8658" }, { "name": { "family": "Iinishi", "given": "Akira" } }, { "name": { "family": "Modaresi", "given": "Seyed Majed" }, "orcid": "0000-0001-9747-9748" }, { "id": "Yoo-Byung-Kuk", "name": { "family": "Yoo", "given": "Byung-Kuk" }, "orcid": "0000-0002-2610-6685" }, { "name": { "family": "Curtis", "given": "Thomas D." } }, { "name": { "family": "Lariviere", "given": "Patrick J." }, "orcid": "0000-0002-8427-3879" }, { "name": { "family": "Liang", "given": "Libang" } }, { "name": { "family": "Son", "given": "Sangkeun" } }, { "name": { "family": "Nicolau", "given": "Samantha" } }, { "name": { "family": "Bargabos", "given": "Rachel" } }, { "name": { "family": "Morrissette", "given": "Madeleine" } }, { "name": { "family": "Gates", "given": "Michael F." } }, { "name": { "family": "Pitt", "given": "Norman" } }, { "name": { "family": "Jakob", "given": "Roman P." } }, { "name": { "family": "Rath", "given": "Parthasarathi" } }, { "name": { "family": "Maier", "given": "Timm" }, "orcid": "0000-0002-7459-1363" }, { "id": "Malyutin-Andrey-G", "name": { "family": "Malyutin", "given": "Andrey G." }, "orcid": "0000-0003-1716-5437" }, { "id": "Kaiser-Jens-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "name": { "family": "Niles", "given": "Samantha" } }, { "name": { "family": "Karavas", "given": "Blake" }, "orcid": "0000-0002-6258-414X" }, { "name": { "family": "Ghiglieri", "given": "Meghan" } }, { "name": { "family": "Bowman", "given": "Sarah E. J." }, "orcid": "0000-0002-7426-7328" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "name": { "family": "Hiller", "given": "Sebastian" }, "orcid": "0000-0002-6709-4684" }, { "name": { "family": "Lewis", "given": "Kim" }, "orcid": "0000-0002-1335-9982" } ] }, "title": "Computational identification of a systemic antibiotic for Gram-negative bacteria", "ispublished": "pub", "full_text_status": "public", "keywords": "Cell Biology; Microbiology (medical); Genetics; Applied Microbiology and Biotechnology; Immunology; Microbiology", "note": "Photorhabdus australis isolates were kindly shared by N. Waterfield at the University of Warwick as well as by A. Thanwisai from Naresuan University.\n\nCrystallization screening at the National Crystallization Center at HWI was supported through NIH grant R24GM141256.\n\nB.-K.Y. thanks L. M. Henling for fruitful discussions. The microED data were collected at the Caltech cryo-EM facility. We thank S. Chen for assistance and the Beckman Institute for their generous support of the cryo-EM facility and the Molecular Observatory at Caltech;\n\nthe Korea Basic Science Institute, Ochang, Korea, for providing NMR (900\u2009MHz) data;\n\nthe staff of beamlines X06DA and X06SA at the Paul Scherrer Institute, Villigen, Switzerland, for support with crystallographic data collection; and the BioEM lab of the University of Basel for support with cryo-EM data acquisition. Calculations were performed at sciCORE (http://scicore.unibas.ch/) scientific computing core facility at the University of Basel.\n\nThis project was supported by the National Institutes of Health grant P01 AI118687 (K.L.), the Swiss National Science Foundation grants 177084 (T.M.) and 187170 (S.H.), and the National Center of Competence in Research AntiResist (180541). \n\nThese authors contributed equally: Ryan D. Miller, Akira Iinishi, Seyed Majed Modaresi, Byung-Kuk Yoo. \n\nContributions. K.L. conceptualized the project; R.D.M., A.I., S.M.M., B.-K.Y., D.C.R., S.H. and K.L. developed the methodology; R.D.M., A.I., S.M.M., B.K.-Y., T.D.C., P.J.L., L.L., S.S., S.N., R.B., M.M., M.F.G., N.P., R.P.J., P.R., T.M., A.G.M., J.T.K., S.N., B.K., M.G., S.B. conducted the investigations; R.D.M., S.M.M., S.H. and K.L. wrote the manuscript; D.C.R., S.H. and K.L. acquired funding; and D.C.R., S.H. and K.L. supervised the project. \n\nData availability. Data supporting the findings of this study are available within the paper and its Supplementary Information, and have been submitted to publicly available databases. Crystal structures are available through PDB: microED dynobactin A structure (7T3H), BamA:dynobactin A X-ray co-crystal (7R1V), BAM complex:dynobactin A cryo-EM (7R1W, EMD-14242). Any other data or datasets from the current study are available upon reasonable request to the corresponding authors. \n\nThe authors declare no competing interests. \n\nPeer review information. Nature Microbiology thanks Paul Hergenrother and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.", "abstract": "Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA. We reasoned that a computational search for genes only distantly related to the darobactin operon may lead to novel compounds. Following this clue, we identified dynobactin A, a novel peptide antibiotic from Photorhabdus australis containing two unlinked rings. Dynobactin is structurally unrelated to darobactins, but also targets BamA. Based on a BamA-dynobactin co-crystal structure and a BAM-complex-dynobactin cryo-EM structure, we show that dynobactin binds to the BamA lateral gate, uniquely protruding into its \u03b2-barrel lumen. Dynobactin showed efficacy in a mouse systemic Escherichia coli infection. This study demonstrates the utility of computational approaches to antibiotic discovery and suggests that dynobactin is a promising lead for drug development.", "date": "2022-10", "date_type": "published", "publication": "Nature Microbiology", "volume": "7", "number": "10", "publisher": "Nature Publishing Group", "pagerange": "1661-1672", "id_number": "CaltechAUTHORS:20221006-438893200.4", "issn": "2058-5276", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221006-438893200.4", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R24GM141256" }, { "agency": "NIH", "grant_number": "P01 AI118687" }, { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "177084" }, { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "187170" }, { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "180541" } ] }, "doi": "10.1038/s41564-022-01227-4", "resource_type": "article", "pub_year": "2022", "author_list": "Miller, Ryan D.; Iinishi, Akira; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0dhfz-8nh58", "eprint_id": 119808, "eprint_status": "archive", "datestamp": "2023-08-22 16:59:56", "lastmod": "2023-10-23 20:08:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Buscagan-Trixia-M", "name": { "family": "Buscagan", "given": "Trixia M." }, "orcid": "0000-0001-8242-9203" }, { "id": "Kaiser-Jens-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Selenocyanate derived Se-incorporation into the nitrogenase Fe protein cluster", "ispublished": "pub", "full_text_status": "public", "keywords": "General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience", "note": "\u00a9 2022, Buscagan et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. \n\nWe dedicate this paper to Prof James B Howard and are grateful for our extensive exchanges on cluster atom exchanges\u2014Jim shaped the way we think about the Fe protein and our journeys with nitrogenase. We also thank Dr Javier Fajardo Jr, Dr Shabman Hematian, and team nitro (Dr Stephanie Threatt, Dr Siobh\u00e1n MacArdle, Dr Rebeccah Warmack and Ailiena Maggiolo) for insightful discussions, Jeffrey Lai for growing Azotobacter vinelandii, and Dr Paul Oyala for EPR training and support. The authors are grateful to the Gordon and Betty Moore Foundation, Don and Judy Voet, and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The Caltech EPR Facility is supported by NSF-1531940. This work was supported by the National Institutes of Health (NIH Grant GM45162) and the Howard Hughes Medical Institute (HHMI). This article is subject to HHMI's Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. \n\nAuthor contributions. Trixia M Buscagan, Conceptualization, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing \u2013 original draft, Writing \u2013 review and editing; Jens T Kaiser, Data curation, Validation, Methodology, Writing \u2013 review and editing; Douglas C Rees, Conceptualization, Supervision, Funding acquisition, Methodology, Project administration, Writing \u2013 review and editing.\n\nThe funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication. \n\nThe authors declare that no competing interests exist.\n\nPublished - elife-79311-v3.pdf
", "abstract": "The nitrogenase Fe protein mediates ATP-dependent electron transfer to the nitrogenase MoFe protein during nitrogen fixation, in addition to catalyzing MoFe protein-independent substrate (CO\u2082) reduction and facilitating MoFe protein metallocluster biosynthesis. The precise role(s) of the Fe protein Fe\u2084S\u2084 cluster in some of these processes remains ill-defined. Herein, we report crystallographic data demonstrating ATP-dependent chalcogenide exchange at the Fe\u2084S\u2084 cluster of the nitrogenase Fe protein when potassium selenocyanate is used as the selenium source, an unexpected result as the Fe protein cluster is not traditionally perceived as a site of substrate binding within nitrogenase. The observed chalcogenide exchange illustrates that this Fe\u2084S\u2084 cluster is capable of core substitution reactions under certain conditions, adding to the Fe protein's repertoire of unique properties.", "date": "2022-07-29", "date_type": "published", "publication": "eLife", "volume": "11", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e79311", "id_number": "CaltechAUTHORS:20230307-198889400.1", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230307-198889400.1", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Don and Judy Voet" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NSF", "grant_number": "CHE-1531940" } ] }, "doi": "10.7554/elife.79311", "primary_object": { "basename": "elife-79311-v3.pdf", "url": "https://authors.library.caltech.edu/records/0dhfz-8nh58/files/elife-79311-v3.pdf" }, "resource_type": "article", "pub_year": "2022", "author_list": "Buscagan, Trixia M.; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/41rhx-h9m88", "eprint_id": 115048, "eprint_status": "archive", "datestamp": "2023-08-20 07:53:07", "lastmod": "2023-10-24 15:17:57", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Warmack-Rebeccah-A", "name": { "family": "Warmack", "given": "Rebeccah A." }, "orcid": "0000-0002-9612-0511" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Anaerobic single particle cryoEM of nitrogenase", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nThe foundational contributions of Dr. Thomas Spatzal and Dr. Belinda Wenke to establishing the anaerobic Vitrobot system and conducting the original cryoEM structures of nitrogenase are gratefully acknowledged. We thank Dr. Jens Kaiser, Dr. Songye Chen, Ailiena Maggiolo, Przemyslaw Dutka, and Dr. James Howard for invaluable discussions. The generous support of the Beckman Institute for the Caltech CryoEM Resource Center was essential for the performance of this research. \n\nThis work was funded by support from the Howard Hughes Medical Institute and NIH grant GM045162 (DCR) and NIH GM143836-01 (RAW). \n\nData and materials availability. The single particle cryoEM maps and models have been deposited into the PDB and EMDB for release upon publication. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.06.04.494841v1.full.pdf
", "abstract": "The enzyme nitrogenase catalyzes the reduction of dinitrogen to ammonia during biological nitrogen fixation through a mechanism involving the ATP dependent interaction of two component proteins adopting multiple conformational states. To date, high resolution structural information has been provided by X-ray crystallography, which restricts the states that can be accessed to those that can be crystallized. Cryo-electron microscopy (cryoEM) presents a new opportunity for structural characterization of nitrogenase solution structures, and may yield new information on the mechanism of nitrogenase by revealing structures of transient or heterogeneous states. In this study, we present single particle cryoEM structures of the MoFe-nitrogenase endogenously isolated from Azotobacter vinelandii. To maintain the fully reduced cluster states of this oxygen sensitive protein, we prepared samples within an anaerobic chamber and employed specialized conditions to minimize partial disordering of the \u03b1-subunit at the air-water interface during freezing. Under these conditions, cryoEM structures of the as-isolated MoFe-protein and stabilized MoFe-protein-Fe-protein ADP-AlF4-complex were generally found to closely resemble their corresponding X-ray crystallographic structures. The cryoEM structures did reveal disordering in regions of the MoFe-protein \u03b1-subunit reminiscent of that observed previously for the \u0394nifB MoFe-protein lacking the FeMo-cofactor, suggesting that this disorder may reflect functionally relevant dynamics, as well as the possibility of asymmetric binding of the Fe-protein to the MoFe-protein in solution. The methods presented here pave the way toward the capture and interrogation of turnover-relevant nitrogenase states by cryoEM.", "date": "2022-06-08", "date_type": "published", "id_number": "CaltechAUTHORS:20220607-424749000", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220607-424749000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Beckman Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "NIH", "grant_number": "GM143836-01" } ] }, "doi": "10.1101/2022.06.04.494841", "primary_object": { "basename": "2022.06.04.494841v1.full.pdf", "url": "https://authors.library.caltech.edu/records/41rhx-h9m88/files/2022.06.04.494841v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Warmack, Rebeccah A. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/37mvw-kze83", "eprint_id": 114670, "eprint_status": "archive", "datestamp": "2023-08-20 07:38:18", "lastmod": "2023-10-24 15:06:38", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Buscagan-Trixia-M", "name": { "family": "Buscagan", "given": "Trixia M." }, "orcid": "0000-0001-8242-9203" }, { "id": "Kaiser-Jens-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Selenocyanate Derived Se-Incorporation into the Nitrogenase Fe Protein Cluster", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. \n\nThis version posted April 30, 2022. \n\nWe dedicate this paper to Prof. James B. Howard and are grateful for our extensive exchanges on cluster atom exchanges\u2014Jim really shaped the way we thought about the Fe protein cluster and our journeys with nitrogenase. We also thank Dr. Javier Fajardo Jr. for insightful discussions, Jeffrey Lai for growing Azotobacter vinelandii, and Dr. Paul Oyala for EPR training and support. The authors are grateful to the Gordon and Betty Moore Foundation, Don and Judy Voet, and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The Caltech EPR Facility is supported by NSF-1531940. This work was supported by the National Institute of Health (NIH Grant GM45162) and the Howard Hughes Medical Institute (HHMI). This article is subject to HHMI's Open Access to Publications policy. \n\nHHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. \n\nThe authors declare no competing financial interests.\n\nSubmitted - 2022.04.29.490034v1.full.pdf
", "abstract": "The nitrogenase Fe protein mediates ATP-dependent electron transfer to the nitrogenase MoFe protein during nitrogen fixation, in addition to catalyzing MoFe protein independent substrate (CO\u2082) reduction and facilitating MoFe protein metallocluster biosynthesis. The precise role(s) of the Fe protein Fe\u2084S\u2084 cluster in some of these processes remains ill-defined. Herein, we report crystallographic data demonstrating ATP-dependent chalcogenide exchange at the Fe\u2084S\u2084 cluster of the nitrogenase Fe protein when potassium selenocyanate is used as the selenium source. The observed chalcogenide exchange illustrates that this Fe\u2084S\u2084 cluster is capable of core substitution reactions under certain conditions, adding to the Fe protein's repertoire of unique properties.", "date": "2022-05-11", "date_type": "published", "id_number": "CaltechAUTHORS:20220511-226093100", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220511-226093100", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Don and Judy Voet" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NSF", "grant_number": "CHE-1531940" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1101/2022.04.29.490034", "primary_object": { "basename": "2022.04.29.490034v1.full.pdf", "url": "https://authors.library.caltech.edu/records/37mvw-kze83/files/2022.04.29.490034v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Buscagan, Trixia M.; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/8zc2m-j8h09", "eprint_id": 112498, "eprint_status": "archive", "datestamp": "2023-08-20 07:21:40", "lastmod": "2023-10-23 15:16:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Glutathione binding to the plant AtAtm3 transporter and implications for the conformational coupling of ABC transporters", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2022 Fan and Rees. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. \n\nReceived: December 6, 2021; Preprint posted: December 14, 2021 (view preprint); Accepted: March 23, 2022; Accepted Manuscript published: March 25, 2022 (version 1); Version of Record published: April 11, 2022 (version 2). \n\nWe thank Andrey Malyutin, Songye Chen, and Corey Hecksel for their support during single-particle cryoEM data collections and the reviewers for their helpful comments, particularly concerning comparisons of AtAtm3 with other ABC transporters. CryoEM was performed in the Beckman Institute Resource Center for cryo-Electron Microscopy at Caltech and at the Stanford-SLAC Cryo-EM Center (S2C2). The S2C2 is supported by the National Institutes of Health Common Fund Transformative High Resolution Cryo-Electron Microscopy program. We thank the Beckman Institute for their support of the cryoEM facility at Caltech. Funding: DCR is a Howard Hughes Medical Institute Investigator. \n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. \n\nAuthor contributions: Chengcheng Fan, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing \u2013 original draft, Writing \u2013 review and editing; Douglas C Rees, Conceptualization,\nFunding acquisition, Methodology, Project administration, Software, Supervision, Writing \u2013 review and editing. \n\nThe authors declare that no competing interests exist. \n\nData availability: The atomic coordinates for inward-facing, inward-facing with GSSG bound, closed and outward-facing conformations were separately deposited in the Protein Data Bank (PDB) and the Electron Microscopy Data Bank (EMDB) with accession codes: PDB 7N58, 7N59, 7N5A and 7N5B; EMDB EMD-24182, EMD-24183, EMD-24184 and EMD-24185. The plasmids encoding full-length AtAtm3 and the AtAtm3 with N-terminal 80 residue deletion were deposited in Addgene with Addgene ID 172321 and 173045, respectively. The raw data for ATPase assays presented in Figure 1 are provided in Source Data 1, while the essdyn.f Fortran source code used for the PCA analysis is provided as Source Code 1.\n\nPublished - elife-76140-v2.pdf
Accepted Version - elife-76140-v1.pdf
Submitted - 2021.12.13.472443v1.full.pdf
Supplemental Material - elife-76140-code1-v2.zip
Supplemental Material - elife-76140-supp1-v2.docx
Supplemental Material - elife-76140-supp2-v2.docx
Supplemental Material - elife-76140-transrepform1-v2.pdf
", "abstract": "The ATP binding cassette (ABC) transporter of mitochondria (Atm) from Arabidopsis thaliana (AtAtm3) has been implicated in the maturation of cytosolic iron-sulfur proteins and heavy metal detoxification, plausibly by exporting glutathione derivatives. Using single-particle cryo-electron microscopy, we have determined four structures of AtAtm3 in three different conformational states: two inward-facing conformations (with and without bound oxidized glutathione [GSSG]), together with closed and outward-facing states stabilized by MgADP-VO4. These structures not only provide a structural framework for defining the alternating access transport cycle, but also reveal the paucity of cysteine residues in the glutathione binding site that could potentially form inhibitory mixed disulfides with GSSG. Despite extensive efforts, we were unable to prepare the ternary complex of AtAtm3 containing both GSSG and MgATP. A survey of structurally characterized type IV ABC transporters that includes AtAtm3 establishes that while nucleotides are found associated with all conformational states, they are effectively required to stabilize occluded, closed, and outward-facing conformations. In contrast, transport substrates have only been observed associated with inward-facing conformations. The absence of structures with dimerized nucleotide binding domains containing both nucleotide and transport substrate suggests that this form of the ternary complex exists only transiently during the transport cycle.", "date": "2022-03-25", "date_type": "published", "publication": "eLife", "volume": "11", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e76140", "id_number": "CaltechAUTHORS:20211217-512156900", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211217-512156900", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.7554/eLife.76140", "pmcid": "PMC9000953", "primary_object": { "basename": "elife-76140-code1-v2.zip", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/elife-76140-code1-v2.zip" }, "related_objects": [ { "basename": "elife-76140-supp1-v2.docx", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/elife-76140-supp1-v2.docx" }, { "basename": "elife-76140-supp2-v2.docx", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/elife-76140-supp2-v2.docx" }, { "basename": "elife-76140-transrepform1-v2.pdf", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/elife-76140-transrepform1-v2.pdf" }, { "basename": "elife-76140-v1.pdf", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/elife-76140-v1.pdf" }, { "basename": "elife-76140-v2.pdf", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/elife-76140-v2.pdf" }, { "basename": "2021.12.13.472443v1.full.pdf", "url": "https://authors.library.caltech.edu/records/8zc2m-j8h09/files/2021.12.13.472443v1.full.pdf" } ], "resource_type": "article", "pub_year": "2022", "author_list": "Fan, Chengcheng and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/bywwr-n0093", "eprint_id": 112322, "eprint_status": "archive", "datestamp": "2023-08-22 14:15:08", "lastmod": "2023-10-23 21:01:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Modeling the stimulation by glutathione of the steady state kinetics of an adenosine triphosphate binding cassette transporter", "ispublished": "pub", "full_text_status": "public", "keywords": "ABC transporter; ATPase activity; glutathione; Michaelis\u2013Menten kinetics; nonessential activator model; Molecular Biology; Biochemistry", "note": "\u00a9 2021 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. \n\nIssue Online: 22 February 2022; Version of Record online: 21 December 2021; Accepted manuscript online: 08 December 2021; Manuscript accepted: 03 December 2021; Manuscript revised: 03 December 2021; Manuscript received: 06 October 2021. \n\nFunding information: Howard Hughes Medical Institute. \n\nAuthor Contributions: Chengcheng Fan: Conceptualization (equal); data curation (lead); formal analysis (equal); investigation (lead); methodology (lead); validation (lead); visualization (lead); writing \u2013 original draft (lead); writing \u2013 review and editing (equal). Douglas C. Rees: Conceptualization (equal); formal analysis (equal); funding acquisition (lead); project administration (lead); supervision (lead); writing \u2013 review and editing (equal). \n\nThe authors declare no competing interests.\n\nPublished - PRO-31-.pdf
Supplemental Material - pro4250-sup-0001-supinfo.pdf
", "abstract": "We report the steady state ATPase activities of the ATP Binding Cassette (ABC) exporter NaAtm1 in the absence and presence of a transported substrate, oxidized glutathione (GSSG), in detergent, nanodiscs, and proteoliposomes. The steady state kinetic data were fit to the \"nonessential activator model\" where the basal ATPase rate of the transporter is stimulated by GSSG. The detailed kinetic parameters varied between the different reconstitution conditions, highlighting the importance of the lipid environment for NaAtm1 function. The increased ATPase rates in the presence of GSSG more than compensate for the modest negative cooperativity observed between MgATP and GSSG in lipid environments. These studies highlight the central role of the elusive ternary complex in accelerating the ATPase rate that is at the heart of coupling mechanism between substrate transport and ATP hydrolysis.", "date": "2022-03", "date_type": "published", "publication": "Protein Science", "volume": "31", "number": "3", "publisher": "Wiley", "pagerange": "752-757", "id_number": "CaltechAUTHORS:20211209-456379000", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211209-456379000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1002/pro.4250", "pmcid": "PMC8862428", "primary_object": { "basename": "PRO-31-.pdf", "url": "https://authors.library.caltech.edu/records/bywwr-n0093/files/PRO-31-.pdf" }, "related_objects": [ { "basename": "pro4250-sup-0001-supinfo.pdf", "url": "https://authors.library.caltech.edu/records/bywwr-n0093/files/pro4250-sup-0001-supinfo.pdf" } ], "resource_type": "article", "pub_year": "2022", "author_list": "Fan, Chengcheng and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ft222-e3n43", "eprint_id": 111334, "eprint_status": "archive", "datestamp": "2023-08-20 06:30:30", "lastmod": "2023-12-22 23:38:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Nichols-Aaron-L", "name": { "family": "Nichols", "given": "Aaron L." }, "orcid": "0000-0001-9341-0049" }, { "id": "Blumenfeld-Zachary", "name": { "family": "Blumenfeld", "given": "Zack" }, "orcid": "0000-0002-4627-5582" }, { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Luebbert-Laura", "name": { "family": "Luebbert", "given": "Laura" }, "orcid": "0000-0003-1379-2927" }, { "id": "Blom-Annet-E-M", "name": { "family": "Blom", "given": "Annet E. M." }, "orcid": "0000-0002-7441-4893" }, { "id": "Cohen-Bruce-N", "name": { "family": "Cohen", "given": "Bruce N." } }, { "id": "Marvin-Jonathan-S", "name": { "family": "Marvin", "given": "Jonathan S." }, "orcid": "0000-0003-2294-4515" }, { "id": "Borden-Philip-M", "name": { "family": "Borden", "given": "Philip M." }, "orcid": "0000-0003-1653-7067" }, { "id": "Kim-Charlene-H", "name": { "family": "Kim", "given": "Charlene H." } }, { "id": "Muthusamy-Anand-K", "name": { "family": "Muthusamy", "given": "Anand K." }, "orcid": "0000-0003-1041-914X" }, { "id": "Shivange-Amol-V", "name": { "family": "Shivange", "given": "Amol V." }, "orcid": "0000-0002-4169-2969" }, { "id": "Knox-Hailey-J", "name": { "family": "Knox", "given": "Hailey J." }, "orcid": "0000-0003-0608-2855" }, { "id": "Rego-Campello-Hugo", "name": { "family": "Rego Campello", "given": "Hugo" }, "orcid": "0000-0001-8588-0198" }, { "id": "Wang-Jonathan-H", "name": { "family": "Wang", "given": "Jonathan H." } }, { "id": "Dougherty-D-A", "name": { "family": "Dougherty", "given": "Dennis A." }, "orcid": "0000-0003-1464-2461" }, { "id": "Looger-Loren-L", "name": { "family": "Looger", "given": "Loren L." }, "orcid": "0000-0002-7531-1757" }, { "id": "Gallagher-Timothy", "name": { "family": "Gallagher", "given": "Timothy" }, "orcid": "0000-0002-3544-327X" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lester-H-A", "name": { "family": "Lester", "given": "Henry A." }, "orcid": "0000-0002-5470-5255" } ] }, "title": "Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2022, Nichols et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. \n\nPreprinted: 04 October 2021; Received: 12 October 2021; Accepted: 03 January 2022; Published: 04 January 2022. \n\nWe thank Stefan Petrovic for his stewardship of the isothermal titration calorimeter in the Caltech Center for Molecular Medicine, Jens Kaiser for help with structural studies at the Caltech Molecular Observatory, the Gradinaru lab and Caltech CLOVER Center for help with viral vectors, and Andres Collazo and Giada Spigolon at the Caltech Biological Imaging Facility. We thank Zoe Beatty, Kallol Bera, Eve Fine, Shan Huang, Elaine Lin, Stephen Mayo, Lin Tian, and Elizabeth Unger for advice and guidance. We thank Achieve Life Sciences for a gift of cytisine. California Tobacco-Related Disease Research Program (TRDRP) (27 FT-0022), ALN. California Tobacco-Related Disease Research Program (TRDRP) (27IP-0057), HAL. California Tobacco-Related Disease Research Program (TRDRP) (T29IR0455), DAD. NIH (GM-123582, DA043829), HAL. NIH (DA049140, GM7616), AKM. Howard\nHughes Medical Institute (LLL, JSM, DCR). UK Engineering and Physical Sciences Research Council (no. EP/N024117/1), TG. Leiden University International Studies Fund (LISF L18020-1-45), LL. \n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. \n\nAuthor contributions: Aaron L Nichols, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Supervision, Validation, Visualization, Writing \u2013 original draft, Writing \u2013 review and editing; Zack Blumenfeld, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing \u2013 review and editing; Chengcheng Fan, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing \u2013 original draft, Writing \u2013 review and editing; Laura Luebbert, Bruce N Cohen, Data curation, Formal analysis, Investigation, Methodology, Writing \u2013 review and editing; Annet EM Blom, Philip M Borden, Conceptualization, Investigation; Jonathan S Marvin, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing \u2013 original draft, Writing \u2013 review and editing; Charlene H Kim, Data curation, Investigation, Methodology, Resources, Writing \u2013 review and editing; Anand K Muthusamy, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Validation, Visualization; Amol V Shivange, Data curation, Validation; Hailey J Knox, Conceptualization, Methodology, Resources, Writing \u2013 review and editing; Hugo Rego Campello, Data curation, Resources, Validation; Jonathan H Wang, Investigation, Methodology, Resources; Dennis A Dougherty, Conceptualization, Data curation, Funding acquisition, Project administration, Resources, Supervision; Loren L Looger, Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing \u2013 review and editing; Timothy Gallagher, Conceptualization, Funding acquisition, Project administration, Supervision, Writing \u2013 review and editing; Douglas C Rees, Data curation, Funding acquisition, Project administration, Supervision, Validation, Writing \u2013 review and editing; Henry A Lester, Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Visualization, Writing \u2013 review and editing. \n\nData availability: The plasmids and associated database entries are available from Addgene (as named in our manuscript) with genetic maps. The Protein Data Bank has published the crystallographics and structural data (accession codes 7S7T, 7S7U, 7S7V). Supplementary File 1 gives relevant details.\n\nPublished - elife-74648-v2.pdf
Accepted Version - elife-74648-v1.pdf
Submitted - 2021.10.04.463082v4.full.pdf
Supplemental Material - elife-74648-supp1-v2.xlsx
Supplemental Material - elife-74648-supp2-v2.xlsx
Supplemental Material - elife-74648-transrepform1-v2.docx
", "abstract": "Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives \u2013 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by >30-fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.", "date": "2022-01-04", "date_type": "published", "publication": "eLife", "volume": "11", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e74648", "id_number": "CaltechAUTHORS:20211008-224629724", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211008-224629724", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "California Tobacco-Related Disease Research Program", "grant_number": "27FT-0022" }, { "agency": "California Tobacco-Related Disease Research Program", "grant_number": "27IP-0057" }, { "agency": "California Tobacco-Related Disease Research Program", "grant_number": "T29IR0455" }, { "agency": "NIH", "grant_number": "GM-123582" }, { "agency": "NIH", "grant_number": "DA043829" }, { "agency": "NIH", "grant_number": "DA049140" }, { "agency": "NIH", "grant_number": "GM7616" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Engineering and Physical Sciences Research Council (EPSRC)", "grant_number": "EP/N024117/1" }, { "agency": "Leiden University", "grant_number": "LISF L18020-1-45" } ] }, "local_group": { "items": [ { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.7554/eLife.74648", "pmcid": "PMC8820738", "primary_object": { "basename": "elife-74648-transrepform1-v2.docx", "url": "https://authors.library.caltech.edu/records/ft222-e3n43/files/elife-74648-transrepform1-v2.docx" }, "related_objects": [ { "basename": "elife-74648-v1.pdf", "url": "https://authors.library.caltech.edu/records/ft222-e3n43/files/elife-74648-v1.pdf" }, { "basename": "elife-74648-v2.pdf", "url": "https://authors.library.caltech.edu/records/ft222-e3n43/files/elife-74648-v2.pdf" }, { "basename": "2021.10.04.463082v4.full.pdf", "url": "https://authors.library.caltech.edu/records/ft222-e3n43/files/2021.10.04.463082v4.full.pdf" }, { "basename": "elife-74648-supp1-v2.xlsx", "url": "https://authors.library.caltech.edu/records/ft222-e3n43/files/elife-74648-supp1-v2.xlsx" }, { "basename": "elife-74648-supp2-v2.xlsx", "url": "https://authors.library.caltech.edu/records/ft222-e3n43/files/elife-74648-supp2-v2.xlsx" } ], "resource_type": "article", "pub_year": "2022", "author_list": "Nichols, Aaron L.; Blumenfeld, Zack; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pgqs4-kb151", "eprint_id": 110783, "eprint_status": "archive", "datestamp": "2023-08-22 11:24:39", "lastmod": "2023-10-23 19:52:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kuznetsova-Anastasiya", "name": { "family": "Kuznetsova", "given": "Anastasiya" } }, { "id": "Masrati-Gal", "name": { "family": "Masrati", "given": "Gal" }, "orcid": "0000-0003-1322-5762" }, { "id": "Vigonsky-Elena", "name": { "family": "Vigonsky", "given": "Elena" } }, { "id": "Livnat-Levanon-Nurit", "name": { "family": "Livnat-Levanon", "given": "Nurit" } }, { "id": "Rose-Jessica", "name": { "family": "Rose", "given": "Jessica" } }, { "id": "Grupper-Moti", "name": { "family": "Grupper", "given": "Moti" } }, { "id": "Baloum-Adan", "name": { "family": "Baloum", "given": "Adan" } }, { "id": "Yang-Janet-G", "name": { "family": "Yang", "given": "Janet G." }, "orcid": "0000-0002-5619-9544" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Ben-Tal-Nir", "name": { "family": "Ben-Tal", "given": "Nir" }, "orcid": "0000-0001-6901-832X" }, { "id": "Lewinson-Oded", "name": { "family": "Lewinson", "given": "Oded" }, "orcid": "0000-0003-4650-0441" } ] }, "title": "Titratable transmembrane residues and a hydrophobic plug are essential for manganese import via the Bacillus anthracis ABC transporter MntBC-A", "ispublished": "pub", "full_text_status": "public", "keywords": "ABC transporter; virulence; transition metals; metal binding; membrane proteins; ATPase", "note": "\u00a9 2021 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC\nBY license (http://creativecommons.org/licenses/by/4.0/). \n\nReceived 9 February 2021, Revised 12 August 2021, Accepted 16 August 2021, Available online 18 August 2021. \n\nThis work was supported by grants from the NATO Science for Peace and Security Program (SPS 625 Project G4622, to O. L. and N. B.-T.), the US-Israel Binational Science Foundation (BSF grant 2015102 to O. L. and D. C. R.), and the Israel Academy of Sciences and Humanities project 1006/18 (to O. L.). \n\nData availability: The data that support the findings of this study are available from the corresponding author upon reasonable request. \n\nAuthor contributions: A. K., E. V., N. L.-L., J. R., M. G., A. B., and O. L. investigation; A. K., J. R., M. G., A. B., and O. L. visualization; G. M. data curation; G. M. formal analysis; G. M., E. V., N. L.-L., and O. L. methodology; N. L.-L., J. G. Y., D. C. R., N. B.-T., and O. L. supervision; J. G. Y., D. C. R., N. B.-T., and O. L. project administration; D. C. R., N. B.-T., and O. L. funding acquisition; O. L. conceptualization; O. L. and N. B.-T. validation; O. L. writing\u2013original draft; O. L. and N. B.-T. writing\u2013review and editing. \n\nThe authors declare that they have no conflicts of interest with the contents of this article.\n\nPublished - 1-s2.0-S0021925821008905-main.pdf
Supplemental Material - 1-s2.0-S0021925821008905-mmc1.pdf
", "abstract": "All extant life forms require trace transition metals (e.g., Fe^(2/3+), Cu^(1/2+), and Mn^(2+)) to survive. However, as these are environmentally scarce, organisms have evolved sophisticated metal uptake machineries. In bacteria, high-affinity import of transition metals is predominantly mediated by ABC transporters. During bacterial infection, sequestration of metal by the host further limits the availability of these ions, and accordingly, bacterial ABC transporters (importers) of metals are key virulence determinants. However, the structure\u2013function relationships of these metal transporters have not been fully elucidated. Here, we used metal-sensitivity assays, advanced structural modeling, and enzymatic assays to study the ABC transporter MntBC-A, a virulence determinant of the bacterial human pathogen Bacillus anthracis. We find that despite its broad metal-recognition profile, MntBC-A imports only manganese, whereas zinc can function as a high-affinity inhibitor of MntBC-A. Computational analysis shows that the transmembrane metal permeation pathway is lined with six titratable residues that can coordinate the positively charged metal, and mutagenesis studies show that they are essential for manganese transport. Modeling suggests that access to these titratable residues is blocked by a ladder of hydrophobic residues, and ATP-driven conformational changes open and close this hydrophobic seal to permit metal binding and release. The conservation of this arrangement of titratable and hydrophobic residues among ABC transporters of transition metals suggests a common mechanism. These findings advance our understanding of transmembrane metal recognition and permeation and may aid the design and development of novel antibacterial agents.", "date": "2021-10", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "297", "number": "4", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "Art. No. 101087", "id_number": "CaltechAUTHORS:20210908-171144390", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210908-171144390", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "North Atlantic Treaty Organization (NATO)", "grant_number": "SPS 625 Project G4622" }, { "agency": "Binational Science Foundation (USA-Israel)", "grant_number": "2015102" }, { "agency": "Israeli Academy of Sciences", "grant_number": "1006/18" } ] }, "doi": "10.1016/j.jbc.2021.101087", "primary_object": { "basename": "1-s2.0-S0021925821008905-main.pdf", "url": "https://authors.library.caltech.edu/records/pgqs4-kb151/files/1-s2.0-S0021925821008905-main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S0021925821008905-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/pgqs4-kb151/files/1-s2.0-S0021925821008905-mmc1.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Kuznetsova, Anastasiya; Masrati, Gal; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/49nfx-ejx73", "eprint_id": 108980, "eprint_status": "archive", "datestamp": "2023-08-20 04:44:09", "lastmod": "2023-10-20 23:19:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Sharaf-Naima-G", "name": { "family": "Sharaf", "given": "Naima G." }, "orcid": "0000-0002-3662-9228" }, { "id": "Shahgholi-Mona", "name": { "family": "Shahgholi", "given": "Mona" } }, { "id": "Kim-Esther", "name": { "family": "Kim", "given": "Esther" } }, { "id": "Lai-Jeffrey-Y", "name": { "family": "Lai", "given": "Jeffrey Y." }, "orcid": "0000-0003-2863-4411" }, { "id": "VanderVelde-D-G", "name": { "family": "VanderVelde", "given": "David G." }, "orcid": "0000-0002-2907-0366" }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that lipidated MetQ is required for interaction", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2021, Sharaf et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.\n\nReceived: 24 April 2021;\nPreprinted: 04 May 2021;\nAccepted: 18 August 2021;\nPublished: 19 August 2021.\n\nWe thank Jacob Parres-Gold and Dr. Sara J Weaver for useful discussions and Dr. Lilien Voong for\ncritical reading of the manuscript. We also thank Dr. Songye Chen and Dr. Andrey Malyutin of the\nBeckman Institute Resource Center for Transmission Electron Microscopy at Caltech for assistance\nwith data collection. This research utilized instrumentation made available by the Caltech CCE Multiuser Mass Spectrometry Laboratory, the CCE Liquids NMR Facility, and the Beckman Institute cryo-EM facility. NGS was supported by the Postdoctoral Enrichment Program from the Burroughs Wellcome Fund and DCR is a Howard Hughes Medical Institute Investigator.\n\nThe funders had no role in study design, data collection and\ninterpretation, or the decision to submit the work for publication.\n\nAuthor Contributions:\nNaima G Sharaf, Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition,\nValidation, Investigation, Visualization, Methodology, Writing - original draft, Project administration,\nWriting - review and editing; Mona Shahgholi, Resources, Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review and editing; Esther Kim, Validation, Investigation,\nMethodology; Jeffrey Y Lai, Software, Methodology; David G VanderVelde, Resources, Methodology; Allen T Lee, Resources, Investigation, Writing - review and editing; Douglas C Rees, Conceptualization, Data curation, Supervision, Funding acquisition, Project administration, Writing - review\nand editing.\n\nThe authors declare that no competing interests exist.\n\nData availability:\nFor NmMetNI in the inward-facing conformation and lipo-NmMetQ:NmMetNI complex in the outward-facing conformation, cryoEM maps have been deposited in the Electron Microscopy Data Bank (EMDB) under accession codes EMD-23752 and EMD-23751. Coordinates for the model are deposited in the Research Collaboratory for Structural Bioinformatics Protein Data Bank under accession numbers 7MC0 and 7MBZ, respectively.\n\nPublished - elife-69742-v2.pdf
Accepted Version - elife-69742-v1.pdf
Submitted - 2021.05.04.442564v1.full.pdf
Supplemental Material - elife-69742-supp-v1.zip
Supplemental Material - elife-69742-transrepform-v2.docx
", "abstract": "NmMetQ is a substrate-binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To elucidate the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the presence and absence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function and localization, playing a role in NmMetNI-mediated transport at the inner membrane and moonlighting on the bacterial surface.", "date": "2021-08-19", "date_type": "published", "publication": "eLife", "volume": "10", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e69742", "id_number": "CaltechAUTHORS:20210506-075107170", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210506-075107170", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Burroughs Wellcome Fund" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.7554/eLife.69742", "pmcid": "PMC8416018", "primary_object": { "basename": "2021.05.04.442564v1.full.pdf", "url": "https://authors.library.caltech.edu/records/49nfx-ejx73/files/2021.05.04.442564v1.full.pdf" }, "related_objects": [ { "basename": "elife-69742-supp-v1.zip", "url": "https://authors.library.caltech.edu/records/49nfx-ejx73/files/elife-69742-supp-v1.zip" }, { "basename": "elife-69742-transrepform-v2.docx", "url": "https://authors.library.caltech.edu/records/49nfx-ejx73/files/elife-69742-transrepform-v2.docx" }, { "basename": "elife-69742-v1.pdf", "url": "https://authors.library.caltech.edu/records/49nfx-ejx73/files/elife-69742-v1.pdf" }, { "basename": "elife-69742-v2.pdf", "url": "https://authors.library.caltech.edu/records/49nfx-ejx73/files/elife-69742-v2.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Sharaf, Naima G.; Shahgholi, Mona; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xxmcb-70q98", "eprint_id": 109270, "eprint_status": "archive", "datestamp": "2023-08-22 10:47:00", "lastmod": "2023-10-23 17:47:11", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Heui-Beom", "name": { "family": "Lee", "given": "Heui Beom" }, "orcid": "0000-0002-9550-2649" }, { "id": "Shiau-Angela-A", "name": { "family": "Shiau", "given": "Angela A." }, "orcid": "0000-0003-4395-9847" }, { "id": "Marchiori-David-A", "name": { "family": "Marchiori", "given": "David A." }, "orcid": "0000-0001-9738-3674" }, { "id": "Oyala-Paul-H", "name": { "family": "Oyala", "given": "Paul H." }, "orcid": "0000-0002-8761-4667" }, { "id": "Yoo-Byung-Kuk", "name": { "family": "Yoo", "given": "Byung-Kuk" }, "orcid": "0000-0002-2610-6685" }, { "id": "Kaiser-Jens-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Britt-R-David", "name": { "family": "Britt", "given": "R. David" }, "orcid": "0000-0003-0889-8436" }, { "id": "Agapie-T", "name": { "family": "Agapie", "given": "Theodor" }, "orcid": "0000-0002-9692-7614" } ] }, "title": "CaMn\u2083^(IV)O\u2084 Cubane Models of the Oxygen Evolving Complex: Spin Ground States S < 9/2 and the Effect of Oxo Protonation", "ispublished": "pub", "full_text_status": "public", "keywords": "electronic structure; magnetic susceptibility; model complexes; oxygen-evolving complex; spin states", "note": "\u00a9 2021 Wiley-VCH GmbH. \n\nIssue Online: 26 July 2021; Version of Record online: 01 July 2021; Accepted manuscript online: 26 May 2021; Manuscript received: 25 April 2021. \n\nThis research was supported by the NIH (R01-GM102687B to T.A.), Dow Next Generation Educator (instrumentation), NSF-1531940 (Caltech EPR facility), the Division of Chemical Sciences, Geosciences, and Biosciences (R.D.B. grant DE-SC0007203) of the Office of Basic Energy Sciences of the U.S. Department of Energy. We thank Dr. Michael\u2005K. Takase and Mr. Lawrence M. Henling at Caltech for assistance with XRD; Dr. Ignacio B. Martini at UCLA for assistance with magnetometry (NSF, MRI-1625776). We thank Andrey Malyutin and Songye Chen for their support during the microED data collection conducted at the Caltech cryoEM facility, and the Beckman Institute at Caltech for their generous support of the cryoEM facility and the Molecular Observatory. \n\nThe authors declare no conflict of interest.\n\nAccepted Version - nihms-1709882.pdf
Supplemental Material - anie202105303-sup-0001-misc_information.pdf
", "abstract": "We report the single crystal XRD and MicroED structure, magnetic susceptibility, and EPR data of a series of CaMn\u2083^(IV)O\u2084 and YMn\u2083^(IV)O\u2084 complexes as structural and spectroscopic models of the cuboidal subunit of the oxygen-evolving complex (OEC). The effect of changes in heterometal identity, cluster geometry, and bridging oxo protonation on the spin-state structure was investigated. In contrast to previous computational models, we show that the spin ground state of CaMn\u2083^(IV)O\u2084 complexes and variants with protonated oxo moieties need not be S = 9/2. Desymmetrization of the pseudo-C\u2083-symmetric Ca(Y)Mn\u2083^(IV)O\u2084 core leads to a lower S = 5/2 spin ground state. The magnitude of the magnetic exchange coupling is attenuated upon oxo protonation, and an S = 3/2 spin ground state is observed in CaMn\u2083^(IV)O\u2083(OH). Our studies complement the observation that the interconversion between the low-spin and high-spin forms of the S\u2082 state is pH-dependent, suggesting that the (de)protonation of bridging or terminal oxygen atoms in the OEC may be connected to spin-state changes.", "date": "2021-08-02", "date_type": "published", "publication": "Angewandte Chemie International Edition", "volume": "60", "number": "32", "publisher": "Wiley", "pagerange": "17671-17679", "id_number": "CaltechAUTHORS:20210527-093456375", "issn": "1433-7851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210527-093456375", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01-GM102687B" }, { "agency": "Dow Next Generation Educator Fund" }, { "agency": "NSF", "grant_number": "CHE-1531940" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-SC0007203" }, { "agency": "NSF", "grant_number": "CHE-1625776" } ] }, "doi": "10.1002/anie.202105303", "pmcid": "PMC8319083", "primary_object": { "basename": "anie202105303-sup-0001-misc_information.pdf", "url": "https://authors.library.caltech.edu/records/xxmcb-70q98/files/anie202105303-sup-0001-misc_information.pdf" }, "related_objects": [ { "basename": "nihms-1709882.pdf", "url": "https://authors.library.caltech.edu/records/xxmcb-70q98/files/nihms-1709882.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Lee, Heui Beom; Shiau, Angela A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1yjap-wtt91", "eprint_id": 109620, "eprint_status": "archive", "datestamp": "2023-08-20 04:27:01", "lastmod": "2023-10-20 23:13:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Probst-Corinna", "name": { "family": "Probst", "given": "Corinna" } }, { "id": "Yang-Jing", "name": { "family": "Yang", "given": "Jing" }, "orcid": "0000-0001-8241-9160" }, { "id": "Krausze-Joern", "name": { "family": "Krausze", "given": "Joern" }, "orcid": "0000-0001-5333-8046" }, { "id": "Hercher-Thomas-W", "name": { "family": "Hercher", "given": "Thomas W." }, "orcid": "0000-0002-1783-1543" }, { "id": "Richers-Casseday-P", "name": { "family": "Richers", "given": "Casseday P." }, "orcid": "0000-0002-1324-0447" }, { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "KC-Khadanand", "name": { "family": "KC", "given": "Khadanand" }, "orcid": "0000-0002-1258-8636" }, { "id": "Giles-Logan-J", "name": { "family": "Giles", "given": "Logan J." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Mendel-Ralf-R", "name": { "family": "Mendel", "given": "Ralf R." }, "orcid": "0000-0003-3785-7764" }, { "id": "Kirk-Martin-L", "name": { "family": "Kirk", "given": "Martin L." }, "orcid": "0000-0002-1479-3318" }, { "id": "Kruse-Tobias", "name": { "family": "Kruse", "given": "Tobias" }, "orcid": "0000-0002-2716-3227" } ] }, "title": "Mechanism of molybdate insertion into pterin-based molybdenum cofactors", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s), under exclusive licence to Springer Nature Limited 2021. \n\nReceived 29 April 2020. Accepted 27 April 2021. Published 28 June 2021. \n\nWe thank A. Calean (TU Braunschweig) for excellent support with inductively coupled plasma mass spectrometry analysis. M.L.K. gratefully acknowledges support of this research by the National Institutes of Health (grant no. GM-057378). M.L.K. and J.Y. thank the UNM Center for Advanced Research Computing, supported in part by the National Science Foundation, for providing the computing resources used in this work. Work at Caltech was supported by the National Institutes of Health (NIH) grant no. GM045162. We acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their support of the Molecular Observatory at Caltech and the staff at beamlines 12-2 and 7-3. M.L.K. and J.Y. acknowledge the Stanford Synchrotron Radiation Lightsource, which is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. R.R.M. and T.K. acknowledge the support of this research by the Deutsche Forschungsgemeinschaft (GRK 2223/1). Correspondence and requests for materials should be addressed to M.L.K. and T.K. \n\nData availability. The protein structure data that support the findings of this study are publicly available from the Protein Data Bank (https://www.rcsb.org/) with accession code 6Q32. We deposited the protein structure along with the structure factor data file that allows for the re-computing and re-evaluation of the structure. Figures 2 and 3 and Supplementary Figs. 3, 4 and Extended Data Fig. 1 are associated with these raw data. Manuscript datasets are available as Supplementary Data files. \n\nThese authors contributed equally: Corinna Probst, Jing Yang, Joern Krausze. \n\nThese authors jointly supervised this work: Martin L. Kirk, Tobias Kruse. \n\nAuthor Contributions. C.P. carried out acquisition, analysis and interpretation of data. J.Y. carried out acquisition, analysis and interpretation of XAS data and computed the reaction coordinate. J.K. analysed and interpreted the data. T.W.H. carried out acquisition, analysis and interpretation of data. C.P.R. synthesized and characterized the trioxo- and dioxo-molybdenum model compounds (2, 3 and 4) and analysed spectroscopic data. T.S. carried out acquisition, analysis and interpretation of data. K.K. assisted with the collection of XAS data. L.J.G. assisted with the collection of XAS data. D.C.R. and R.R.M. revised the manuscript. M.L.K. conceived the idea, performed design analysis and interpretation of the data, and drafted the manuscript. T.K. conceived the idea and design, analysed and interpreted the data, and drafted the manuscript. All authors discussed the results and commented on the manuscript. \n\nThe authors declare no competing interests. \n\nPeer review information. Nature Chemistry thanks Partha Basu, Carola Schulzke and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.\n\nAccepted Version - nihms-1698257.pdf
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", "abstract": "The molybdenum cofactor (Moco) is found in the active site of numerous important enzymes that are critical to biological processes. The bidentate ligand that chelates molybdenum in Moco is the pyranopterin dithiolene (molybdopterin, MPT). However, neither the mechanism of molybdate insertion into MPT nor the structure of Moco prior to its insertion into pyranopterin molybdenum enzymes is known. Here, we report this final maturation step, where adenylated MPT (MPT\u2013AMP) and molybdate are the substrates. X-ray crystallography of the Arabidopsis thaliana Mo-insertase variant Cnx1E S269D D274S identified adenylated Moco (Moco\u2013AMP) as an unexpected intermediate in this reaction sequence. X-ray absorption spectroscopy revealed the first coordination sphere geometry of Moco trapped in the Cnx1E active site. We have used this structural information to deduce a mechanism for molybdate insertion into MPT\u2013AMP. Given their high degree of structural and sequence similarity, we suggest that this mechanism is employed by all eukaryotic Mo-insertases.", "date": "2021-08", "date_type": "published", "publication": "Nature Chemistry", "volume": "13", "number": "8", "publisher": "Nature Publishing Group", "pagerange": "758-765", "id_number": "CaltechAUTHORS:20210628-180924312", "issn": "1755-4330", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210628-180924312", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM057378" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "GRK 2223/1" } ] }, "doi": "10.1038/s41557-021-00714-1", "pmcid": "PMC8325642", "primary_object": { "basename": "41557_2021_714_MOESM17_ESM.txt", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM17_ESM.txt" }, "related_objects": [ { "basename": "41557_2021_714_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM2_ESM.pdf" }, { "basename": "41557_2021_714_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM3_ESM.pdf" }, { "basename": "41557_2021_714_MOESM4_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM4_ESM.pdf" }, { "basename": "41557_2021_714_MOESM12_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM12_ESM.pdf" }, { "basename": "41557_2021_714_MOESM11_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM11_ESM.pdf" }, { "basename": "41557_2021_714_MOESM14_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM14_ESM.pdf" }, { "basename": "41557_2021_714_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM1_ESM.pdf" }, { "basename": "41557_2021_714_MOESM6_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM6_ESM.pdf" }, { "basename": "41557_2021_714_MOESM7_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM7_ESM.pdf" }, { "basename": "41557_2021_714_MOESM10_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM10_ESM.pdf" }, { "basename": "nihms-1698257.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/nihms-1698257.pdf" }, { "basename": "41557_2021_714_Fig6_ESM.jpg", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_Fig6_ESM.jpg" }, { "basename": "41557_2021_714_MOESM15_ESM.txt", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM15_ESM.txt" }, { "basename": "41557_2021_714_MOESM16_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM16_ESM.pdf" }, { "basename": "41557_2021_714_MOESM18_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM18_ESM.pdf" }, { "basename": "41557_2021_714_MOESM5_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM5_ESM.pdf" }, { "basename": "41557_2021_714_MOESM8_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM8_ESM.pdf" }, { "basename": "41557_2021_714_MOESM9_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM9_ESM.pdf" }, { "basename": "41557_2021_714_MOESM13_ESM.pdf", "url": "https://authors.library.caltech.edu/records/1yjap-wtt91/files/41557_2021_714_MOESM13_ESM.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Probst, Corinna; Yang, Jing; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tyhnc-fxv47", "eprint_id": 107199, "eprint_status": "archive", "datestamp": "2023-08-22 09:12:56", "lastmod": "2023-10-23 15:38:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Buscagan-Trixia-M", "name": { "family": "Buscagan", "given": "Trixia M." }, "orcid": "0000-0001-8242-9203" }, { "id": "Perez-Kathryn-A", "name": { "family": "Perez", "given": "Kathryn A." }, "orcid": "0000-0003-1707-5060" }, { "id": "Maggiolo-Ailiena-O", "name": { "family": "Maggiolo", "given": "Ailiena O." }, "orcid": "0000-0003-1707-5060" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" } ] }, "title": "Structural Characterization of Two CO Molecules Bound to the Nitrogenase Active Site", "ispublished": "pub", "full_text_status": "public", "keywords": "carbonyl ligands; C\u2212C coupling; cofactors; nitrogenases; X-ray diffraction", "note": "\u00a9 2020 The Authors. Angewandte Chemie published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. \n\nIssue Online: 01 March 2021; Version of Record online: 27 January 2021; Accepted manuscript online: 15 December 2020; Manuscript received: 25 November 2020. \n\nWe thank the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech. We thank Prof. James\u2005B. Howard, Dr. Rebeccah Warmack, Dr. Renee Arias, Dr. Belinda Wenke, Dr. Stephanie Threatt, and Siobh\u00e1n MacArdle for insightful discussions, Dr. Jens Kaiser for support of crystallographic data collection, Jeffrey Lai for growing Azotobacter vinelandii, and Dr. Paul Oyala for EPR training and support. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE\u2010AC02\u201076SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). This research was supported by the National Institute of Health (NIH Grant GM45162) and the Howard Hughes Medical Institute. The Caltech EPR Facility is supported by NSF\u20101531940. \n\nThe authors declare no conflict of interest.\n\nPublished - anie.202015751.pdf
Supplemental Material - anie202015751-sup-0001-misc_information.pdf
", "abstract": "As an approach towards unraveling the nitrogenase mechanism, we have studied the binding of CO to the active\u2010site FeMo\u2010cofactor. CO is not only an inhibitor of nitrogenase, but it is also a substrate, undergoing reduction to hydrocarbons (Fischer\u2013Tropsch\u2010type chemistry). The C\u2212C bond forming capabilities of nitrogenase suggest that multiple CO or CO\u2010derived ligands bind to the active site. Herein, we report a crystal structure with two CO ligands coordinated to the FeMo\u2010cofactor of the molybdenum nitrogenase at 1.33\u2005\u00c5 resolution. In addition to the previously observed bridging CO ligand between Fe2 and Fe6 of the FeMo\u2010cofactor, a new ligand binding mode is revealed through a second CO ligand coordinated terminally to Fe6. While the relevance of this state to nitrogenase\u2010catalyzed reactions remains to be established, it highlights the privileged roles for Fe2 and Fe6 in ligand binding, with multiple coordination modes available depending on the ligand and reaction conditions.", "date": "2021-03-08", "date_type": "published", "publication": "Angewandte Chemie International Edition", "volume": "60", "number": "11", "publisher": "Wiley", "pagerange": "5704-5707", "id_number": "CaltechAUTHORS:20201218-102813715", "issn": "1433-7851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201218-102813715", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NSF", "grant_number": "DMR-1531940" } ] }, "doi": "10.1002/anie.202015751", "pmcid": "PMC7920927", "primary_object": { "basename": "anie.202015751.pdf", "url": "https://authors.library.caltech.edu/records/tyhnc-fxv47/files/anie.202015751.pdf" }, "related_objects": [ { "basename": "anie202015751-sup-0001-misc_information.pdf", "url": "https://authors.library.caltech.edu/records/tyhnc-fxv47/files/anie202015751-sup-0001-misc_information.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Buscagan, Trixia M.; Perez, Kathryn A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qtd3c-mxw25", "eprint_id": 107957, "eprint_status": "archive", "datestamp": "2023-08-22 08:56:44", "lastmod": "2023-10-23 16:21:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cho-Hye-Jin", "name": { "family": "Cho", "given": "Hye Jin" } }, { "id": "Kim-Kyung-su", "name": { "family": "Kim", "given": "Kyung-su" } }, { "id": "Kim-Hyunwoo", "name": { "family": "Kim", "given": "Hyunwoo" } }, { "id": "Kim-Taewoo", "name": { "family": "Kim", "given": "Taewoo" } }, { "id": "Malyutin-Andrey-G", "name": { "family": "Malyutin", "given": "Andrey G." }, "orcid": "0000-0003-1716-5437" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Yoo-Byung-Kuk", "name": { "family": "Yoo", "given": "Byung-Kuk" }, "orcid": "0000-0002-2610-6685" }, { "id": "Song-Changsik", "name": { "family": "Song", "given": "Changsik" }, "orcid": "0000-0003-4754-1843" } ] }, "title": "Microcrystal Electron Diffraction Elucidates Water-Specific Polymorphism-Induced Emission Enhancement of Bis-arylacylhydrazone", "ispublished": "pub", "full_text_status": "public", "keywords": "MicroED; AIE; hydrazone; polymorphism; CIEE", "note": "\u00a9 2021 American Chemical Society. \n\nReceived: November 30, 2020; Accepted: January 24, 2021; Published: February 5, 2021. \n\nThis work was supported by the Nano Material Development Program (2012M3A7B4049677) and the Basic Science Research Program (2019R1A2C1004256) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT, Republic of Korea. This research was also supported partially by the Howard Hughes Medical Institute. B.-K.Y. thanks Lawrence M. Henling and Chih-Te Zee for crystallographic assistance as well as Dr. Oh-Hoon Kwon (during his sabbatical stay at Caltech) and Dr. Jens Kaiser for fruitful discussions. C. S. thanks Prof. Jin Yong Lee, Jong Hyeon Lim, and Hyun Dong Kim for their assistance in computational calculations. \n\nAuthor Contributions. H.J.C. and K.S.K. contributed equally to this study. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. \n\nThe authors declare no competing financial interest.\n\nSupplemental Material - am0c21248_si_001.pdf
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Supplemental Material - am0c21248_si_004.mp4
", "abstract": "Aggregation-induced emission (AIE) phenomena have gained intense interest over the last decades because of its importance in solid-state emission. However, the elucidation of a working mechanism is difficult owing to the limited characterization methods on solid-state molecules, further complicated if dynamic structural changes occur. Here, a series of bis-arylacylhydrazones (BAHs) were synthesized, for which their AIE properties are only turned on by the reversible adsorption of water molecules. We used microcrystal electron diffraction (MicroED) to determine the molecular structures of two BAHs directly from bulk powders (without attempting to grow crystals) prepared in the absence or presence of water adsorption. This study reveals the unambiguous characterization of the dependence of crystal packing on the specific cocrystallization with hydrates. The structural analysis demonstrates that water molecules form strong hydrogen bonds with three neighboring BAH-1, resulting in the almost complete planarization and restriction of the intramolecular rotation of the molecule. MicroED plays an important role in providing a decisive clue for the reversible polymorphism changes induced by the adsorption of water molecules, regulating emissive properties.", "date": "2021-02-17", "date_type": "published", "publication": "ACS Applied Materials & Interfaces", "volume": "13", "number": "6", "publisher": "American Chemical Society", "pagerange": "7546-7555", "id_number": "CaltechAUTHORS:20210208-144010742", "issn": "1944-8244", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210208-144010742", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Research Foundation of Korea", "grant_number": "2012M3A7B4049677" }, { "agency": "National Research Foundation of Korea", "grant_number": "2019R1A2C1004256" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1021/acsami.0c21248", "primary_object": { "basename": "am0c21248_si_001.pdf", "url": "https://authors.library.caltech.edu/records/qtd3c-mxw25/files/am0c21248_si_001.pdf" }, "related_objects": [ { "basename": "am0c21248_si_002.cif", "url": "https://authors.library.caltech.edu/records/qtd3c-mxw25/files/am0c21248_si_002.cif" }, { "basename": "am0c21248_si_003.cif", "url": "https://authors.library.caltech.edu/records/qtd3c-mxw25/files/am0c21248_si_003.cif" }, { "basename": "am0c21248_si_004.mp4", "url": "https://authors.library.caltech.edu/records/qtd3c-mxw25/files/am0c21248_si_004.mp4" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Cho, Hye Jin; Kim, Kyung-su; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fwyd5-mrn93", "eprint_id": 105139, "eprint_status": "archive", "datestamp": "2023-08-22 06:20:41", "lastmod": "2023-10-23 17:20:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal structure of the Escherichia coli transcription termination factor Rho", "ispublished": "pub", "full_text_status": "public", "keywords": "membrane-protein purification; crystallization contaminant; transcription termination factor; cryoEM", "note": "\u00a9 2020 International Union of Crystallography. \n\nReceived 7 April 2020; Accepted 31 July 2020. \n\nThe following funding is acknowledged: Howard Hughes Medical Institute.\n\nPublished - pg5087.pdf
", "abstract": "During the crystal structure analysis of an ATP-binding cassette (ABC) transporter overexpressed in Escherichia coli, a contaminant protein was crystallized. The identity of the contaminant was revealed by mass spectrometry to be the Escherichia coli transcription terminator factor Rho, structures of which had been previously determined in different conformational states. Although Rho was present at only \u223c1% of the target protein (a bacterial homolog of the eukaryotic ABC transporter of mitochondria from Novosphingobium aromaticivorans; NaAtm1), it preferentially crystallized in space group C2 as thin plates that diffracted to 3.30\u2005\u00c5 resolution. The structure of Rho in this crystal form exhibits a hexameric open-ring staircase conformation with bound ATP; this characteristic structure was also observed on electron-microscopy grids of the NaAtm1 preparation.", "date": "2020-09-01", "date_type": "published", "publication": "Acta Crystallographica Section F: Structural Biology and Crystallization Communications", "volume": "76", "number": "9", "publisher": "International Union of Crystallography", "pagerange": "Art. No. F76", "id_number": "CaltechAUTHORS:20200828-111354696", "issn": "2053-230X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200828-111354696", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1107/s2053230x20010572", "pmcid": "PMC7470046", "primary_object": { "basename": "pg5087.pdf", "url": "https://authors.library.caltech.edu/records/fwyd5-mrn93/files/pg5087.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Fan, Chengcheng and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b2a5f-v7t90", "eprint_id": 104556, "eprint_status": "archive", "datestamp": "2023-08-22 06:02:05", "lastmod": "2023-12-08 00:18:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A structural framework for unidirectional transport by a bacterial ABC exporter", "ispublished": "pub", "full_text_status": "public", "keywords": "ATP-binding cassette transporters; ABC transporters; alternating access mechanism; glutathione transport; transport cycle", "note": "\u00a9 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). \n\nContributed by Douglas C. Rees, May 28, 2020 (sent for review April 7, 2020; reviewed by Susan K. Buchanan and Dirk-Jan Slotboom). PNAS first published July 23, 2020. \n\nWe thank the staffs of the Stanford Synchrotron Radiation Lightsource (SSRL) beamline 12-2 and of the Advanced Photon Source GM/CA beamline for support during X-ray diffraction data collection; Paul Adams, Kaspar Locher, Oded Lewinson, Gabriele Meloni, William Clemons, the organizers and speakers at the Cold Spring Harbor X-ray Method in Structural Biology Course (2018), the CCP4/APS School for Macromolecular Crystallography (2017), and the SBGrid/NE-CAT Phenix Workshop (2016) for discussions; Haoqing Wang, Andrey Malyutin, Songye Chen, and Megan Meyer for their support during single-particle cryo-EM data collection; and the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, under contract no. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE of Biological and Environmental Research and by the NIH National Institute of General Medical Sciences (NIGMS) (Grant P41GM103393). GM/CA@APS was funded in whole or in part by federal funds from the National Cancer Institute (Grant ACB-12002) and the NIGMS (Grant AGM-12006). This research used resources of the Advanced Photon Source, a DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. The Eiger 16M detector was funded by NIH Office of Research Infrastructure Programs High-End Instrumentation Grant 1S10OD012289-01A1. The cryo-EM was performed in the Beckman Institute Resource Center for Transmission Electron Microscopy at Caltech and at the Stanford SLAC Cryo-EM Center (S2C2). The S2C2 is supported by the NIH Health Common Fund Transformative High Resolution Cryo-Electron Microscopy program. \n\nAuthor contributions: C.F. and D.C.R. designed research; C.F. performed research; C.F., J.T.K., and D.C.R. analyzed data; and C.F. and D.C.R. wrote the paper. \n\nReviewers: S.K.B., National Institutes of Health; and D.-J.S., University of Groningen. \n\nThe authors declare no competing interest. \n\nData deposition: Data for this article have been deposited in the RCSB Protein Data Bank under IDs 6PAM, 6PAN, 6PAO, 6PAQ, 6PAR, 6VQT, and 6VQU. The two cryo-EM single-particle structures in nanodiscs have also been deposited in the Electron Microscopy Data Bank under accession codes EMD-21356 (NaAtm1-MgADPVO4) and EMD-21357 (NaAtm1). \n\nThis article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2006526117/-/DCSupplemental.\n\nPublished - 19228.full.pdf
Supplemental Material - pnas.2006526117.sapp.pdf
", "abstract": "The ATP-binding cassette (ABC) transporter of mitochondria (Atm1) mediates iron homeostasis in eukaryotes, while the prokaryotic homolog from Novosphingobium aromaticivorans (NaAtm1) can export glutathione derivatives and confer protection against heavy-metal toxicity. To establish the structural framework underlying the NaAtm1 transport mechanism, we determined eight structures by X-ray crystallography and single-particle cryo-electron microscopy in distinct conformational states, stabilized by individual disulfide crosslinks and nucleotides. As NaAtm1 progresses through the transport cycle, conformational changes in transmembrane helix 6 (TM6) alter the glutathione-binding site and the associated substrate-binding cavity. Significantly, kinking of TM6 in the post-ATP hydrolysis state stabilized by MgADPVO\u2084 eliminates this cavity, precluding uptake of glutathione derivatives. The presence of this cavity during the transition from the inward-facing to outward-facing conformational states, and its absence in the reverse direction, thereby provide an elegant and conceptually simple mechanism for enforcing the export directionality of transport by NaAtm1. One of the disulfide crosslinked NaAtm1 variants characterized in this work retains significant glutathione transport activity, suggesting that ATP hydrolysis and substrate transport by Atm1 may involve a limited set of conformational states with minimal separation of the nucleotide-binding domains in the inward-facing conformation.", "date": "2020-08-11", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "117", "number": "32", "publisher": "National Academy of Sciences", "pagerange": "19228-19236", "id_number": "CaltechAUTHORS:20200724-090008939", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200724-090008939", "funders": { "items": [ { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "ACB-12002" }, { "agency": "NIH", "grant_number": "AGM-12006" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-06CH11357" }, { "agency": "NIH", "grant_number": "1S10OD012289-01A1" } ] }, "doi": "10.1073/pnas.2006526117", "pmcid": "PMC7430982", "primary_object": { "basename": "19228.full.pdf", "url": "https://authors.library.caltech.edu/records/b2a5f-v7t90/files/19228.full.pdf" }, "related_objects": [ { "basename": "pnas.2006526117.sapp.pdf", "url": "https://authors.library.caltech.edu/records/b2a5f-v7t90/files/pnas.2006526117.sapp.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Fan, Chengcheng; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/swqj6-17f29", "eprint_id": 103924, "eprint_status": "archive", "datestamp": "2023-08-19 21:57:46", "lastmod": "2023-10-20 16:51:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Einsle-Oliver", "name": { "family": "Einsle", "given": "Oliver" }, "orcid": "0000-0001-8722-2893" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural Enzymology of Nitrogenase Enzymes", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2020 American Chemical Society. \n\nReceived: January 26, 2020; Publication Date: June 15, 2020. \n\nThis article is part of the Reactivity of Nitrogen from the Ground to the Atmosphere special issue. \n\nResearch in the Einsle group was supported by Deutsche Forschungsgemeinschaft, RTG 1976 (project ID 235777276) and PP 1927 (project ID 273919336) and the European Research Council (grant no. 310656). Research in the Rees group was supported by US National Institutes of Health grant GM045162 and the Howard Hughes Medical Institute. Stimulating discussions with James B. Howard and members of the Einsle and Rees research groups are gratefully acknowledged. \n\nThe authors declare no competing financial interest.\n\nAccepted Version - nihms-1754447.pdf
", "abstract": "The reduction of dinitrogen to ammonia by nitrogenase reflects a complex choreography involving two component proteins, MgATP and reductant. At center stage of this process resides the active site cofactor, a complex metallocluster organized around a trigonal prismatic arrangement of iron sites surrounding an interstitial carbon. As a consequence of the choreography, electrons and protons are delivered to the active site for transfer to the bound N\u2082. While the detailed mechanism for the substrate reduction remains enigmatic, recent developments highlight the role of hydrides and the privileged role for two irons of the trigonal prism in the binding of exogenous ligands. Outstanding questions concern the precise nature of the intermediates between N\u2082 and NH\u2083, and whether the cofactor undergoes significant rearrangement during turnover; resolution of these issues will require the convergence of biochemistry, structure, spectroscopy, computation, and model chemistry.", "date": "2020-06-24", "date_type": "published", "publication": "Chemical Reviews", "volume": "120", "number": "12", "publisher": "American Chemical Society", "pagerange": "4969-5004", "id_number": "CaltechAUTHORS:20200615-133406983", "issn": "0009-2665", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200615-133406983", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "RTG 1976" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "235777276" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "PP 1927" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "273919336" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1021/acs.chemrev.0c00067", "pmcid": "PMC8606229", "primary_object": { "basename": "nihms-1754447.pdf", "url": "https://authors.library.caltech.edu/records/swqj6-17f29/files/nihms-1754447.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Einsle, Oliver and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/vezvm-wdv47", "eprint_id": 101206, "eprint_status": "archive", "datestamp": "2023-08-19 19:56:05", "lastmod": "2023-12-13 16:59:12", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Borden-P-M", "name": { "family": "Borden", "given": "Philip M." } }, { "id": "Shivange-A-V", "name": { "family": "Shivange", "given": "Amol V." } }, { "id": "Lester-H-A", "name": { "family": "Lester", "given": "Henry A." }, "orcid": "0000-0002-5470-5255" }, { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A fast genetically encoded fluorescent sensor for faithful in vivo acetylcholine detection in mice, fish, worms and flies", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nbioRxiv preprint first posted online Feb. 8, 2020. \n\nWe would like to thank Deepika Walpita (Janelia) for rat neuronal culture, and Kim Ritola (Janelia) for making AAV virus. We thank Jens T. Kaiser at the Caltech Molecular Observatory and the beamline staff at SSRL 12-2 for their support during data collection. DD and HK thank Dr. Martin Fuhrmann (DZNE, Bonn, Germany) for help with virus injections. \n\nThis work was supported by the Howard Hughes Medical Institute. JJZ is supported by NIH NS104670, PZ by an Alzheimer's Association research fellowship, CPF by NIH NS95809, PKZ by a 2019 International Science and Engineering Fair award, WSZ by a 2019 Harrison undergraduate research award, and GW by Epilepsy Foundation postdoctoral fellowship No. 310443. JJZ is the Radboud Professor and Sir Yue-Kong Pao Chair Professor. HAL and AVS are supported by NIH DA037161, NIH DA043829, California Tobacco-Related Disease Research Program 23XT-0007 and 27IP-0057, and NARSAD. JSD is supported by R01-GM095674. JFC is supported by NIH DA022340, and AF by a STAR-PREP fellowship. LL is supported by a National Natural Science Foundation of China grant NSFC81771284. We gratefully acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the NIH, NIGMS (P41GM103393). BSK is supported by NIH (NS111583, DA047444, MH104069). DD and HK are supported by DFG (SPP1757, SFB1089, DI853/3-5) and BONFOR to DD. WBG is supported by NIH R01 NS047325. ES is supported by JSPS KAKENHI #15KK0340. \n\nAuthor contributions: P.M.B., P.Z., H.A.L., J.J.Z., and L.L.L. led the project. P.M.B., A.V.S., J.S.M., H.A.L., and L.L.L. performed protein engineering. P.M.B., A.V.S., and J.S.M. performed biochemical characterization. P.M.B., J.S.M., C.F., D.C.R. acquired and refined crystal structures. P.M.B., A.A., and R.P. performed spectroscopy. P.M.B. and J.S.M. performed HEK293 and cultured neuron experiments. P.Z. and Y.Z. screened sensor variants in brain slice. P.Z., P.K.Z., Y.Z., W.S.Z., G.W., and B.X. acquired and analyzed nanoscopic imaging data. P.Z., Y.Z., L.G., G.-X.Z., K.G., and L.L. made Sindbis and lentivirus constructs and live virus. P.Z. and Y.Z. performed other slice characterization. H.K. and D.D. performed hippocampal stratum radiatum slice characterization. E.S. and B.S.K. performed hippocampal astrocyte slice characterization. Y.C., A.G.Y., and C.P.F. performed striatal slice characterization. J.S.D. acquired and analyzed the C. elegans data. C.D. and V.J. acquired and analyzed the Drosophila data. M.T. and M.K. acquired and analyzed the zebrafish data. O.N. and K.P. did SLAP imaging and experiments on the effects of anesthesia. J.C. and W.-B.G. did motor cortex experiments. A.F. and J.F.C. did hippocampal reward experiments. P.M.B., H.A.L., J.J.Z., and L.L.L. wrote the paper, with help from all authors. \n\nCode availability: All analysis code used in this study is available upon request. \n\nData availability: All data from this study is available upon request. \n\nAccession codes: All constructs have been deposited at Addgene (#137950-137959). Sequences have been deposited in Genbank. PDB accession code for iAChSnFR0.4 is 6URU. PDB accession code for the binding protein-only component of iAChSnFR is 6V1R. AAV virus is available from Addgene. \n\nThe authors declare no competing financial interests.\n\nSubmitted - 2020.02.07.939504v1.full.pdf
", "abstract": "Here we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice and in vivo preparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all organisms.", "date": "2020-02-10", "date_type": "published", "id_number": "CaltechAUTHORS:20200210-132609996", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200210-132609996", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "NS104670" }, { "agency": "Alzheimer's Association" }, { "agency": "NIH", "grant_number": "NS95809" }, { "agency": "Harvard University" }, { "agency": "University of Virginia" }, { "agency": "Epilepsy Foundation of America", "grant_number": "310443" }, { "agency": "NIH", "grant_number": "DA037161" }, { "agency": "NIH", "grant_number": "DA043829" }, { "agency": "California Tobacco-Related Disease Research Program", "grant_number": "23XT-0007" }, { "agency": "California Tobacco-Related Disease Research Program", "grant_number": "27IP-0057" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "NIH", "grant_number": "R01-GM095674" }, { "agency": "NIH", "grant_number": "DA022340" }, { "agency": "University of Maryland" }, { "agency": "National Natural Science Foundation of China", "grant_number": "81771284" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "NS111583" }, { "agency": "NIH", "grant_number": "DA047444" }, { "agency": "NIH", "grant_number": "MH104069" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "SPP1757" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "SFB1089" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "DI853/3-5" }, { "agency": "BONFOR-Forschungsf\u00f6rderprogramm" }, { "agency": "NIH", "grant_number": "R01 NS047325" }, { "agency": "Japan Society for the Promotion of Science (JSPS)", "grant_number": "15KK0340" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2020.02.07.939504", "primary_object": { "basename": "2020.02.07.939504v1.full.pdf", "url": "https://authors.library.caltech.edu/records/vezvm-wdv47/files/2020.02.07.939504v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2020", "author_list": "Borden, Philip M.; Shivange, Amol V.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4gdcv-hkt63", "eprint_id": 99227, "eprint_status": "archive", "datestamp": "2023-08-22 03:01:21", "lastmod": "2023-10-18 17:59:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Buscagan-Trixia-M", "name": { "family": "Buscagan", "given": "Trixia M." }, "orcid": "0000-0001-8242-9203" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Rethinking the Nitrogenase Mechanism: Activating the Active Site", "ispublished": "pub", "full_text_status": "public", "keywords": "nitrogenase; nitrogen fixation mechanism; iron-sulfur clusters; transition metal catalysts", "note": "\u00a9 2019 Elsevier Inc. \n\nAvailable online 10 October 2019. \n\nWe thank Professor James B. Howard, Professor Jonas C. Peters, Dr. Thomas Spatzal, Professor Markus Ribbe, Professor Yilin Hu, Ailiena Maggiolo, Dr. Rebeccah Warmack, Javier Fajardo, Jr., and Professor Shabnam Hematian for insightful discussions and NIH grant GM045162 for funding. \n\nAuthor Contributions: T.M.B. wrote the manuscript, and T.M.B. and D.C.R. revised the manuscript.\n\nAccepted Version - nihms-1545332.pdf
", "abstract": "Biological nitrogen fixation, the conversion of dinitrogen (N\u2082) to ammonia (NH\u2083) catalyzed by nitrogenases (N\u2082ases), provides Earth with \u223c50% of its bioavailable nitrogen. Without N\u2082 fixation, the chemically inert N\u2082 that comprises 80% of the Earth's atmosphere would not be accessible to life. Although the reduction of N\u2082 to NH\u2083 is thermodynamically favored at ambient conditions, both the biological and industrial N\u2082 fixation processes have a significant energy requirement. Understanding the catalytic mechanism of N\u2082ase may lead to the development of new catalysts that can operate under mild conditions in water closer to equilibrium. \n\nMost catalysts for N\u2082-to-NH\u2083 fixation, whether homogeneous, heterogeneous, or biological, contain transition metal centers that bind N\u2082 to lower the kinetic barrier for reduction. Exemplifying this theme, the active site cofactor of N\u2082ase contains eight transition metals. Although the N\u2082ase active site must become highly reactive during the catalytic cycle, the cofactor in the as-isolated state of N\u2082ase is a stable species that does not bind N\u2082. Consequently, cofactor activation is required prior to N\u2082 binding and functionalization. Herein, we discuss potential routes for cofactor activation based on recent studies of the Mo and V N\u2082ases. Like other transition metal systems capable of N\u2082 reduction, such as the Mittasch catalyst used in the Haber-Bosch process, structural rearrangements to the catalyst precursor are required to generate metal centers sufficiently reactive enough to bind N\u2082. Characterization of the activated state(s) of the cofactor that binds N\u2082 and the structural rearrangements constituting cofactor activation/deactivation processes will be key to establishing the mechanism of biological N\u2082 fixation. These mechanistic insights will be important for guiding the development of new catalysts or improved reaction conditions for N_2 reduction with more favorable energetic requirements than current processes.", "date": "2019-11-20", "date_type": "published", "publication": "Joule", "volume": "3", "number": "11", "publisher": "Cell Press", "pagerange": "2662-2678", "id_number": "CaltechAUTHORS:20191010-160259916", "issn": "2542-4351", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191010-160259916", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM045162" } ] }, "doi": "10.1016/j.joule.2019.09.004", "pmcid": "PMC7451245", "primary_object": { "basename": "nihms-1545332.pdf", "url": "https://authors.library.caltech.edu/records/4gdcv-hkt63/files/nihms-1545332.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Buscagan, Trixia M. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ctt4r-4zn75", "eprint_id": 99761, "eprint_status": "archive", "datestamp": "2023-08-19 18:42:04", "lastmod": "2023-10-18 18:45:33", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fan-Chengcheng", "name": { "family": "Fan", "given": "Chengcheng" }, "orcid": "0000-0003-4213-5758" }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crosslinking of nucleotide binding domains improves the coupling efficiency of an ABC transporter", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. \n\nbioRxiv preprint first posted online Nov. 9, 2019. \n\nAuthor contributions: C.F. and D.C.R designed the research; C.F. performed the research; C.F., J.T.K and D.C.R. analyzed the data; and C.F and D.C.R prepared the manuscript. \n\nThe authors declare no competing interests. \n\nData availability: Atomic coordinates were deposited in the Protein Data Bank with accession codes 6PAM (NaA527C-MgADP), 6PAN (NaS526C-ATP), 6PAO (NaT525C-ATP), 6PAQ (NaE523Q-ATP) and 6PAR (NaAtm1-MgAMPPNP). The raw data for ATPase and transport assays that support the findings in Figure 2 and Table 2 are included in Table S6, and all the other data are available from the corresponding author upon reasonable request. \n\nWe thank the beamline staffs of the Stanford Synchrotron Radiation Lightsource\nbeamline 12-2 and of the Advanced Photon Source GM/CA beamline for support during data collection. Discussions with Paul Adams, Gabriele Meloni, William Clemons, the organizers and speakers at the Cold Spring Harbor X-ray Method in Structural Biology Course (2018), the CCP4/APS School for Macromolecular Crystallography (2017) and the SBGrid/NE-CAT Phenix Workshop (2016) are gratefully acknowledged. We thank the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). GM/CA@APS has been funded in whole or in part with Federal funds from the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. The Eiger 16M detector was funded by an NIH\u2013Office of Research Infrastructure Programs, High-End Instrumentation Grant (1S10OD012289-01A1).\n\nSubmitted - 836676.full.pdf
Supplemental Material - media-1.pdf
Supplemental Material - media-2.pdf
", "abstract": "ATP Binding Cassette (ABC) transporters often exhibit significant basal ATPase activity in the absence of transported substrates. To investigate the factors that contribute to this inefficient coupling of ATP hydrolysis to transport, we characterized the structures and functions of variants of the bacterial Atm1 homolog from Novosphingobium aromaticivorans (NaAtm1), including forms with disulfide crosslinks between the nucleotide binding domains. Unexpectedly, disulfide crosslinked variants of NaAtm1 reconstituted into proteoliposomes not only transported oxidized glutathione, but also exhibited more efficient coupling of ATP hydrolysis to GSSG transport than the native transporter. These observations suggest that enhanced conformational dynamics of reconstituted NaAtm1 may contribute to the inefficient use of ATP. Understanding the origins of this uncoupled ATPase activity, and reducing the impact through disulfide crosslinking or other protocols, will be critical for the detailed dissection of ABC transporter mechanism to assure that the ATP dependent steps are indeed relevant to substrate translocation.", "date": "2019-11-12", "date_type": "published", "id_number": "CaltechAUTHORS:20191111-072609203", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191111-072609203", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "ACB-12002" }, { "agency": "NIH", "grant_number": "AGM-12006" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-06CH11357" }, { "agency": "NIH", "grant_number": "1S10OD012289-01A1" }, { "agency": "National Cancer Institute" }, { "agency": "National Institute of General Medical Sciences" } ] }, "doi": "10.1101/836676", "primary_object": { "basename": "836676.full.pdf", "url": "https://authors.library.caltech.edu/records/ctt4r-4zn75/files/836676.full.pdf" }, "related_objects": [ { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/ctt4r-4zn75/files/media-1.pdf" }, { "basename": "media-2.pdf", "url": "https://authors.library.caltech.edu/records/ctt4r-4zn75/files/media-2.pdf" } ], "resource_type": "monograph", "pub_year": "2019", "author_list": "Fan, Chengcheng; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/vhqmf-gc030", "eprint_id": 97442, "eprint_status": "archive", "datestamp": "2023-08-22 02:35:05", "lastmod": "2023-10-18 15:57:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Nguyen-Phong-T", "name": { "family": "Nguyen", "given": "Phong T." } }, { "id": "Lai-Jeffrey-Y", "name": { "family": "Lai", "given": "Jeffrey Y." } }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structures of the Neisseria meningitides methionine\u2010binding protein MetQ in substrate-free form and bound to L- and D-methionine isomers", "ispublished": "pub", "full_text_status": "public", "keywords": "ABC transporters; D\u2010methionine; L\u2010methionine; MetNI methionine importer; periplasmic binding protein MetQ", "note": "\u00a9 2019 The Authors. Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. \n\nAccepted manuscript online: 26 July 2019; Manuscript accepted:\n18 July 2019; Manuscript revised: 17 July 2019; Manuscript received: 30 June 2019. \n\nA Vietnam International Education Development scholarship from the Vietnam Ministry of Education and Training to P.T.N. is gratefully acknowledged. We thank Dr. Chad Brautigam and Dr. Shih\u2010chia (Scott) Tso for assistance with ITC, and Christoph M\u00fcller for his assistance in the initial phases of this project. We gratefully acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech, and the staff at Beamline 12\u20132, Stanford Synchrotron Radiation Lightsource (SSRL) for their assistance with data collection. SSRL is operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393). We thank the Center for Environmental Microbial Interactions for their support of microbiology research at Caltech. D.C.R. is an investigator in Howard Hughes Medical Institute. \n\nAuthor Contributions: P.T.N. and D.C.R. designed experiments, analyzed data, and wrote the manuscript. P.T.N. performed the experiments. J.Y.L. contributed to the design and performance of experiments. J.T.K. contributed to the X\u2010ray crystallographic data analysis. \n\nThe authors declare no conflict of interest.\n\nPublished - Nguyen_et_al-2019-Protein_Science.pdf
", "abstract": "The bacterial periplasmic methionine\u2010binding protein MetQ is involved in the import of methionine by the cognate MetNI methionine ABC transporter. The MetNIQ system is one of the few members of the ABC importer family that has been structurally characterized in multiple conformational states. Critical missing elements in the structural analysis of MetNIQ are the structure of the substrate\u2010free form of MetQ, and detailing how MetQ binds multiple methionine derivatives, including both L\u2010 and D\u2010methionine isomers. In this study, we report the structures of the Neisseria meningitides MetQ in substrate\u2010free form and in complexes with L\u2010methionine and with D\u2010methionine, along with the associated binding constants determined by isothermal titration calorimetry. Structures of the substrate\u2010free (N238A) and substrate\u2010bound N. meningitides MetQ are related by a \"Venus\u2010fly trap\" hinge\u2010type movement of the two domains accompanying methionine binding and dissociation. L\u2010methionine and D\u2010methionine bind to the same site on MetQ, and this study emphasizes the important role of asparagine 238 in ligand binding and affinity. A thermodynamic analysis demonstrates that ligand\u2010free MetQ associates with the ATP bound form of MetNI ~40 times more tightly than does liganded MetQ, consistent with the necessity of dissociating methionine from MetQ for transport to occur.", "date": "2019-10", "date_type": "published", "publication": "Protein Science", "volume": "28", "number": "10", "publisher": "Wiley", "pagerange": "1750-1757", "id_number": "CaltechAUTHORS:20190726-102347763", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190726-102347763", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Training (Vietnam)" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1002/pro.3694", "pmcid": "PMC6739813", "primary_object": { "basename": "Nguyen_et_al-2019-Protein_Science.pdf", "url": "https://authors.library.caltech.edu/records/vhqmf-gc030/files/Nguyen_et_al-2019-Protein_Science.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Nguyen, Phong T.; Lai, Jeffrey Y.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/bnba3-1gz34", "eprint_id": 97491, "eprint_status": "archive", "datestamp": "2023-08-19 17:29:23", "lastmod": "2023-10-18 15:59:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Henthorn-Justin-T", "name": { "family": "Henthorn", "given": "Justin T." }, "orcid": "0000-0003-4876-2680" }, { "id": "Arias-Renee-J", "name": { "family": "Arias", "given": "Renee J." }, "orcid": "0000-0002-6505-7513" }, { "id": "Koroidov-Sergey", "name": { "family": "Koroidov", "given": "Sergey" } }, { "id": "Kroll-Thomas", "name": { "family": "Kroll", "given": "Thomas" } }, { "id": "Sokaras-Dimosthenis", "name": { "family": "Sokaras", "given": "Dimosthenis" } }, { "id": "Bergmann-Uwe", "name": { "family": "Bergmann", "given": "Uwe" }, "orcid": "0000-0001-5639-166X" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "DeBeer-Serena", "name": { "family": "DeBeer", "given": "Serena" }, "orcid": "0000-0002-5196-3400" } ] }, "title": "Localized Electronic Structure of Nitrogenase FeMoco Revealed by Selenium K-edge High Resolution X-ray Absorption Spectroscopy", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. \n\nReceived: July 2, 2019; Published: July 29, 2019. \n\nJ.T.H. and S.D. thank the Max Planck Society for funding. S.D. acknowledges funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 615414 and the DFG SPP 1927 \"Iron Sulfur for Life\" project (Project No. DE 1877/1-1). J.T.H. acknowledges funding from the Alexander von Humboldt Foundation. S.K. would like to thank The Knut and Alice Wallenberg Foundation (KAW 2014.0370) for financial support. We are grateful to Dr. T. Weyherm\u00fcller and T. Mu\u00dffeldt for supplying [Et4N]2[Fe2Se2(SPh)4]. We thank the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech, the staff of SSRL BL12-2 for their technical assistance. Support from NIH Grant GM045162 and the Howard Hughes Medical Institute to D.C.R. and from NIH Training Grant T32GM7616 to R.J.A. is gratefully acknowledged. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. We thank Paul Oyala and the Electron Paramagnetic Resonance Facility at Caltech for assistance with EPR measurements. \n\nAuthor Contributions: J.T.H. and R.J.A. contributed equally. \n\nThe authors declare no competing financial interest. \n\nCrystallographic data has been uploaded to the PDB.\n\nPublished - jacs.9b06988.pdf
Supplemental Material - ja9b06988_si_001.pdf
", "abstract": "The size and complexity of Mo-dependent nitrogenase, a multicomponent enzyme capable of reducing dinitrogen to ammonia, have made a detailed understanding of the FeMo cofactor (FeMoco) active site electronic structure an ongoing challenge. Selective substitution of sulfur by selenium in FeMoco affords a unique probe wherein local Fe\u2013Se interactions can be directly interrogated via high-energy resolution fluorescence detected X-ray absorption spectroscopic (HERFD XAS) and extended X-ray absorption fine structure (EXAFS) studies. These studies reveal a significant asymmetry in the electronic distribution of the FeMoco, suggesting a more localized electronic structure picture than is typically assumed for iron\u2013sulfur clusters. Supported by experimental small molecule model data in combination with time dependent density functional theory (TDDFT) calculations, the HERFD XAS data is consistent with an assignment of Fe2/Fe6 as an antiferromagnetically coupled diferric pair. HERFD XAS and EXAFS have also been applied to Se-substituted CO-inhibited MoFe protein, demonstrating the ability of these methods to reveal electronic and structural changes that occur upon substrate binding. These results emphasize the utility of Se HERFD XAS and EXAFS for selectively probing the local electronic and geometric structure of FeMoco.", "date": "2019-08-28", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "141", "number": "34", "publisher": "American Chemical Society", "pagerange": "13676-13688", "id_number": "CaltechAUTHORS:20190729-142108096", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190729-142108096", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Max Planck Society" }, { "agency": "European Research Council (ERC)", "grant_number": "615414" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "SPP 1927" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "DE 1877/1-1" }, { "agency": "Alexander von Humboldt Foundation" }, { "agency": "Knut and Alice Wallenberg Foundation", "grant_number": "KAW 2014.0370" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM7616" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" } ] }, "doi": "10.1021/jacs.9b06988", "pmcid": "PMC6716209", "primary_object": { "basename": "jacs.9b06988.pdf", "url": "https://authors.library.caltech.edu/records/bnba3-1gz34/files/jacs.9b06988.pdf" }, "related_objects": [ { "basename": "ja9b06988_si_001.pdf", "url": "https://authors.library.caltech.edu/records/bnba3-1gz34/files/ja9b06988_si_001.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Henthorn, Justin T.; Arias, Renee J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jqmnc-51033", "eprint_id": 92551, "eprint_status": "archive", "datestamp": "2023-08-22 01:10:10", "lastmod": "2023-10-20 15:50:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wenke-Belinda-B", "name": { "family": "Wenke", "given": "Belinda B." }, "orcid": "0000-0003-3214-6197" }, { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Site-specific oxidation state assignments of the irons in the [4Fe:4S]^(2+/1+/0) states of the nitrogenase Fe-protein", "ispublished": "pub", "full_text_status": "public", "keywords": "nitrogenase; iron sulphur cluster; metalloprotein crystallography; multiwavelength anomalous diffraction", "note": "\u00a9 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co.\nKGaA. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. \n\nAccepted manuscript online: 30 January 2019; Manuscript accepted: 18 January 2019; Manuscript received: 14 December 2018. \n\nWe thank Prof. O. Einsle, Prof. L. Zhang, Dr. K. Perez, Dr. R. Arias, A. Maggiolo, and Prof. J.\u2005B. Howard for informative discussions, and K.\u2005H. Lee for the initial identification of the ADP\u2010bound Fe\u2010protein crystals. We acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech. We thank the staff at Beamline 12\u20102, Stanford Synchrotron Radiation Lightsource (SSRL), operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393), and the NCRR (P41RR001209). We also thank Dr. A. Di\u2005Bilio for assisting with EPR experiments. The Caltech EPR Facility was supported by NSF\u20101531940. This work was supported by NIH grant GM045162 and the Howard Hughes Medical Institute. \n\nThe authors declare no conflict of interest.\n\nPublished - Wenke_et_al-2019-Angewandte_Chemie_International_Edition.pdf
Supplemental Material - anie201813966-sup-0001-misc_information.pdf
", "abstract": "The nitrogenase iron protein (Fe\u2010protein) contains an unusual [4Fe:4S] iron\u2010sulphur cluster that is stable in three oxidation states: 2+, 1+, and 0. Here, we use spatially resolved anomalous dispersion (SpReAD) refinement to determine oxidation assignments for the individual irons for each state. Additionally, we report the 1.13\u2010\u00c5 resolution structure for the ADP bound Fe\u2010protein, the highest resolution Fe\u2010protein structure presently determined. In the dithionite\u2010reduced [4Fe:4S]^(1+) state, our analysis identifies a solvent exposed, delocalized Fe2.5+ pair and a buried Fe^(2+) pair. We propose that ATP binding by the Fe\u2010protein promotes an internal redox rearrangement such that the solvent\u2010exposed Fe pair becomes reduced, thereby facilitating electron transfer to the nitrogenase molybdenum iron\u2010protein. In the [4Fe:4S]^0 and [4Fe:4S]^(2+) states, the SpReAD analysis supports oxidation states assignments for all irons in these clusters of Fe^(2+) and valence delocalized Fe^(2.5+), respectively.", "date": "2019-03-18", "date_type": "published", "publication": "Angewandte Chemie International Edition", "volume": "58", "number": "12", "publisher": "Wiley", "pagerange": "3894-3897", "id_number": "CaltechAUTHORS:20190201-083038828", "issn": "1433-7851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190201-083038828", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "NSF", "grant_number": "CHE-1531940" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1002/anie.201813966", "pmcid": "PMC6519357", "primary_object": { "basename": "Wenke_et_al-2019-Angewandte_Chemie_International_Edition.pdf", "url": "https://authors.library.caltech.edu/records/jqmnc-51033/files/Wenke_et_al-2019-Angewandte_Chemie_International_Edition.pdf" }, "related_objects": [ { "basename": "anie201813966-sup-0001-misc_information.pdf", "url": "https://authors.library.caltech.edu/records/jqmnc-51033/files/anie201813966-sup-0001-misc_information.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Wenke, Belinda B.; Spatzal, Thomas; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/cx7sf-95355", "eprint_id": 92244, "eprint_status": "archive", "datestamp": "2023-08-19 13:50:01", "lastmod": "2023-10-20 22:08:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fisher-A-J", "name": { "family": "Fisher", "given": "Aaron J." }, "orcid": "0000-0001-9754-4618" }, { "id": "Mendoza-Denton-R", "name": { "family": "Mendoza-Denton", "given": "Rodolfo" } }, { "id": "Patt-C", "name": { "family": "Patt", "given": "Colette" } }, { "id": "Young-Ira", "name": { "family": "Young", "given": "Ira" } }, { "id": "Eppig-A", "name": { "family": "Eppig", "given": "Andrew" } }, { "id": "Garrell-R-L", "name": { "family": "Garrell", "given": "Robin L." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Nelson-T-W", "name": { "family": "Nelson", "given": "Tenea W." } }, { "id": "Richards-M-A", "name": { "family": "Richards", "given": "Mark A." } } ] }, "title": "Structure and belonging: Pathways to success for underrepresented minority and women PhD students in STEM fields", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 Fisher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nReceived: August 1, 2018; Accepted: December 3, 2018; Published: January 9, 2019. \n\nData Availability Statement: All data necessary for replicating the path model are included with the paper and its Supporting Information files. The provided data is insufficient for replicating the\ndescriptive information of this study (e.g. participation by department), as this data is potentially identifying and cannot be shared publicly. Researchers interested in investigating or replicating our descriptive statistics can contact the Office for Protection of Human Subjects at the University of California, Berkeley: Office for Protection of Human Subjects, University of California, Berkeley, 1608 Fourth Street, Suite 220, Berkeley CA, 94710-5940. Phone: 510-642-7461. \n\nThis research is supported by the National Science Foundation (nsf.gov) under Award Numbers 1647273, 1306595, 1306683, 1306747, 1306760 to M.A.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. \n\nThe authors have declared that no competing interests exist.\n\nAuthor Contributions: \nConceptualization: Aaron J. Fisher.\nData curation: Andrew Eppig.\nFormal analysis: Aaron J. Fisher.\nFunding acquisition: Rodolfo Mendoza-Denton, Colette Patt, Robin L. Garrell, Douglas C.\nRees, Tenea W. Nelson, Mark A. Richards.\nInvestigation: Mark A. Richards.\nMethodology: Aaron J. Fisher, Andrew Eppig.\nProject administration: Rodolfo Mendoza-Denton, Colette Patt, Ira Young, Robin L. Garrell,\nDouglas C. Rees, Tenea W. Nelson, Mark A. Richards.\nWriting \u2013 original draft: Aaron J. Fisher, Rodolfo Mendoza-Denton.\nWriting \u2013 review & editing: Aaron J. Fisher, Rodolfo Mendoza-Denton, Colette Patt, Ira\nYoung, Andrew Eppig, Robin L. Garrell, Douglas C. Rees, Tenea W. Nelson, Mark A.\nRichards.\n\nPublished - journal.pone.0209279.pdf
Supplemental Material - journal.pone.0209279.s001.xlsx
", "abstract": "The advancement of underrepresented minority and women PhD students to elite postdoctoral and faculty positions in the STEM fields continues to lag that of majority males, despite decades of efforts to mitigate bias and increase opportunities for students from diverse backgrounds. In 2015, the National Science Foundation Alliance for Graduate Education and the Professoriate (NSF AGEP) California Alliance (Berkeley, Caltech, Stanford, UCLA) conducted a wide-ranging survey of graduate students across the mathematical, physical, engineering, and computer sciences in order to identify levers to improve the success of PhD students, and, in time, improve diversity in STEM leadership positions, especially the professoriate. The survey data were interpreted via path analysis, a method that identifies significant relationships, both direct and indirect, among various factors and outcomes of interest. We investigated two important outcomes: publication rates, which largely determine a new PhD student's competitiveness in the academic marketplace, and subjective well-being. Women and minority students who perceived that they were well-prepared for their graduate courses and accepted by their colleagues (faculty and fellow students), and who experienced well-articulated and structured PhD programs, were most likely to publish at rates comparable to their male majority peers. Women PhD students experienced significantly higher levels of distress than their male peers, both majority and minority, while both women and minority student distress levels were mitigated by clearly-articulated expectations, perceiving that they were well-prepared for graduate level courses, and feeling accepted by their colleagues. It is unclear whether higher levels of distress in women students is related directly to their experiences in their STEM PhD programs. The findings suggest that mitigating factors that negatively affect diversity should not, in principle, require the investment of large resources, but rather requires attention to the local culture and structure of individual STEM PhD programs.", "date": "2019-01-09", "date_type": "published", "publication": "PLoS ONE", "volume": "14", "number": "1", "publisher": "Public Library of Science", "pagerange": "Art. No. e0209279", "id_number": "CaltechAUTHORS:20190114-090253242", "issn": "1932-6203", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190114-090253242", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "HRD-1647273" }, { "agency": "NSF", "grant_number": "HRD-1306595" }, { "agency": "NSF", "grant_number": "HRD-1306683" }, { "agency": "NSF", "grant_number": "HRD-1306747" }, { "agency": "NSF", "grant_number": "HRD-1306760" } ] }, "doi": "10.1371/journal.pone.0209279", "pmcid": "PMC6326412", "primary_object": { "basename": "journal.pone.0209279.pdf", "url": "https://authors.library.caltech.edu/records/cx7sf-95355/files/journal.pone.0209279.pdf" }, "related_objects": [ { "basename": "journal.pone.0209279.s001.xlsx", "url": "https://authors.library.caltech.edu/records/cx7sf-95355/files/journal.pone.0209279.s001.xlsx" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Fisher, Aaron J.; Mendoza-Denton, Rodolfo; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3d89y-2s020", "eprint_id": 90370, "eprint_status": "archive", "datestamp": "2023-08-22 00:17:30", "lastmod": "2023-10-18 23:24:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Nguyen-Phong-T", "name": { "family": "Nguyen", "given": "Phong T." } }, { "id": "Lai-Jeffrey-Y", "name": { "family": "Lai", "given": "Jeffrey Y." } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Kaiser-Jens-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter", "ispublished": "pub", "full_text_status": "public", "keywords": "ATP Binding Cassette transporter; alternating access transport; mechanism; methionine transporter; transinhibition", "note": "\u00a9 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). \n\nContributed by Douglas C. Rees, August 26, 2018 (sent for review June 26, 2018; reviewed by Bert Poolman and Nieng Yan). PNAS published ahead of print October 23, 2018. \n\nData and Materials Availability: Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, with PDB ID code 6CVL. The MetNI and MetQ constructs have been deposited with Addgene, with IDs 118269 (N295A E166Q MetNI) and 118268 (N229A MetQ) for the structural work, and IDs 118253, 118254, 118256\u2013118261 and 118581 for the transport assay (Table 1). \n\nWe thank Dr. Raymond Liu for critical reading of the manuscript and Dr. Nathan Dalleska and Stefan Petrovic for assistance with ICP-MS and ITC, respectively. A Vietnam International Education Development scholarship from the Vietnam Ministry of Education and Training (to P.T.N.) is gratefully acknowledged. We gratefully acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech and the staff at Beamline 12-2, SSRL, for their assistance with data collection. SSRL is operated for the US Department of Energy and supported by its Office of Biological and Environmental Research and by the NIH, National Institute of General Medical Sciences (P41GM103393), and the National Center for Research Resources (P41RR001209). We thank the Center for Environmental Microbial Interactions for their support of microbiology research at Caltech. D.C.R. is an investigator at Howard Hughes Medical Institute. \n\nAuthor contributions: P.T.N. and D.C.R. designed research; P.T.N., J.Y.L., A.T.L., and J.T.K. performed research; P.T.N., J.Y.L., and A.T.L. contributed new reagents/analytic tools; P.T.N., J.Y.L., A.T.L., J.T.K., and D.C.R. analyzed data; and P.T.N. and D.C.R. wrote the paper. \n\nReviewers: B.P., University of Groningen; and N.Y., Princeton University. \n\nThe authors declare no conflict of interest. \n\nData deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.wwpdb.org (PDB ID code 6CVL). The MetNI and MetQ constructs generated in this work have been deposited in Addgene [ID codes 118268 (N229A MetQ) and 118269 (N295A E166Q MetNI) for the structural work, and ID codes 118253, 118254, 118256\u2013118261, and 118581 for the transport assay]. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1811003115/-/DCSupplemental.\n\nPublished - E10596.full.pdf
Supplemental Material - pnas.1811003115.sapp.pdf
", "abstract": "The Escherichia coli methionine ABC transporter MetNI exhibits both high-affinity transport toward L-methionine and broad specificity toward methionine derivatives, including D-methionine. In this work, we characterize the transport of D-methionine derivatives by the MetNI transporter. Unexpectedly, the N229A substrate-binding deficient variant of the cognate binding protein MetQ was found to support high MetNI transport activity toward D-selenomethionine. We determined the crystal structure at 2.95 \u00c5 resolution of the ATP\u03b3S-bound MetNIQ complex in the outward-facing conformation with the N229A apo MetQ variant. This structure revealed conformational changes in MetQ providing substrate access through the binding protein to the transmembrane translocation pathway. MetQ likely mediates uptake of methionine derivatives through two mechanisms: in the methionine-bound form delivering substrate from the periplasm to the transporter (the canonical mechanism) and in the apo form by facilitating ligand binding when complexed to the transporter (the noncanonical mechanism). This dual role for substrate-binding proteins is proposed to provide a kinetic strategy for ABC transporters to transport both high- and low-affinity substrates present in a physiological concentration range.", "date": "2018-11-06", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "number": "45", "publisher": "National Academy of Sciences", "pagerange": "E10596-E10604", "id_number": "CaltechAUTHORS:20181023-130948201", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181023-130948201", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Training (Vietnam)" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1073/pnas.1811003115", "pmcid": "PMC6233128", "primary_object": { "basename": "E10596.full.pdf", "url": "https://authors.library.caltech.edu/records/3d89y-2s020/files/E10596.full.pdf" }, "related_objects": [ { "basename": "pnas.1811003115.sapp.pdf", "url": "https://authors.library.caltech.edu/records/3d89y-2s020/files/pnas.1811003115.sapp.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Nguyen, Phong T.; Lai, Jeffrey Y.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/9x80k-mks55", "eprint_id": 90068, "eprint_status": "archive", "datestamp": "2023-08-19 11:50:58", "lastmod": "2023-10-18 23:10:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Herrera-Nadia", "name": { "family": "Herrera", "given": "Nadia" }, "orcid": "0000-0003-4157-9429" }, { "id": "Maksaev-Grigory", "name": { "family": "Maksaev", "given": "Grigory" }, "orcid": "0000-0001-6242-1634" }, { "id": "Haswell-Elizabeth-S", "name": { "family": "Haswell", "given": "Elizabeth S." }, "orcid": "0000-0002-4246-065X" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived: 13 July 2018. Accepted: 31 August 2018. Published online: 01 October 2018. \n\nWe thank Troy Walton, Chinenye (Chinny) Idigo, Jens Kaiser and Jeff Abramson for enlightening discussions and the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech. X-ray crystallography data was collected at the Stanford Synchrotron Radiation Lightsource (SSRL), a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility operated by the United States Department of Energy, by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (P41GM103393) and the National Center for Research Resources, Biomedical Technology Program (P41RR001209). This research was funded in part by the National Institutes of Health National Institute of General Medical Sciences (5R01GM084211-07) and the Howard Hughes Medical Institute. N.H. was also independently funded by the Howard Hughes Medical Institute Gilliam Fellowship. Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, with PDBID 6CTD. \n\nAuthor Contributions: N.H., G.M., E.H., D.C.R. conceptualized the approach and developed the experimental protocols. N.H. purified, crystallized and solved the crystal structure and with D.C.R. analyzed the structure. G.M. performed and with E.H. analyzed the electrophysiology experiments. N.H. wrote the initial manuscript draft, and N.H., G.M., E.H., D.C.R. revised and edited the manuscript. All authors read and approved the final manuscript. \n\nThe authors declare no competing interests.\n\nPublished - s41598-018-32536-6.pdf
Supplemental Material - 41598_2018_32536_MOESM1_ESM.pdf
", "abstract": "Microbial survival in dynamic environments requires the ability to successfully respond to abrupt changes in osmolarity. The mechanosensitive channel of large conductance (MscL) is a ubiquitous channel that facilitates the survival of bacteria and archaea under severe osmotic downshock conditions by relieving excess turgor pressure in response to increased membrane tension. A prominent structural feature of MscL, the cytoplasmic C-terminal domain, has been suggested to influence channel assembly and function. In this report, we describe the X-ray crystal structure and electrophysiological properties of a C-terminal domain truncation of the Mycobacterium tuberculosis MscL (MtMscL\u0394C). A crystal structure of MtMscL\u0394C solubilized in the detergent n-dodecyl-\u03b2-D-maltopyranoside reveals the pentameric, closed state-like architecture for the membrane spanning region observed in the previously solved full-length MtMscL. Electrophysiological characterization demonstrates that MtMscL\u0394C retains mechanosensitivity, but with conductance and tension sensitivity more closely resembling full length EcMscL than MtMscL. This study establishes that the C-terminal domain of MtMscL is not required for oligomerization of the full-length channel, but rather influences the tension sensitivity and conductance properties of the channel. The collective picture that emerges from these data is that each MscL channel structure has characteristic features, highlighting the importance of studying multiple homologs.", "date": "2018-10-01", "date_type": "published", "publication": "Scientific Reports", "volume": "8", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 14566", "id_number": "CaltechAUTHORS:20181001-113521133", "issn": "2045-2322", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181001-113521133", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "NIH", "grant_number": "5R01GM084211-07" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1038/s41598-018-32536-6", "pmcid": "PMC6167328", "primary_object": { "basename": "41598_2018_32536_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/9x80k-mks55/files/41598_2018_32536_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "s41598-018-32536-6.pdf", "url": "https://authors.library.caltech.edu/records/9x80k-mks55/files/s41598-018-32536-6.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Herrera, Nadia; Maksaev, Grigory; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gc25g-j3s49", "eprint_id": 88357, "eprint_status": "archive", "datestamp": "2023-08-22 00:05:32", "lastmod": "2023-10-18 22:00:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Arias-Renee-J", "name": { "family": "Arias", "given": "Renee J." }, "orcid": "0000-0002-6505-7513" }, { "id": "Kaiser-Jens-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The \"speed limit\" for macromolecular crystal growth", "ispublished": "pub", "full_text_status": "public", "keywords": "protein crystallization; enzyme mechanism; protein nanocrystals; micro\u2010electron diffraction", "note": "\u00a9 2018 The Authors. Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. \n\nReceived 17 June 2018; Accepted 27 July 2018; First published: 28 July 2018. \n\nWe thank the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their support of the Molecular Observatory at Caltech. We thank Pamela Bjorkman for use of the Leica microscope used in this study. Support from the Howard Hughes Medical Institute Collaborative Innovation Award (Axel Brunger, Stanford, Lead Investigator), NIH Grant GM045162 (DCR) and from NIH Training Grant T32GM7616 to RJA is gratefully acknowledged. \n\nThe authors declare no conflict of interest.\n\nPublished - Arias_et_al-2018-Protein_Science.pdf
", "abstract": "A simple \"diffusion\u2010to\u2010capture\" model is used to estimate the upper limit to the growth rate of macromolecular crystals under conditions when the rate limiting process is the mass transfer of sample from solution to the crystal. Under diffusion\u2010limited crystal growth conditions, this model predicts that the cross\u2010sectional area of a crystal will increase linearly with time; this prediction is validated by monitoring the growth rate of lysozyme crystals. A consequence of this analysis is that when crystal growth is diffusion\u2010limited, micron\u2010sized crystals can be produced in ~1 s, which would be compatible with the turnover time of many enzymes. Consequently, the ability to record diffraction patterns from sub\u2010micron sized crystals by X\u2010ray Free Electron Lasers and micro\u2010electron diffraction technologies opens the possibility of trapping intermediate enzyme states by crystallization.", "date": "2018-10", "date_type": "published", "publication": "Protein Science", "volume": "27", "number": "10", "publisher": "Wiley", "pagerange": "1837-1841", "id_number": "CaltechAUTHORS:20180730-115724719", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180730-115724719", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM7616" } ] }, "doi": "10.1002/pro.3491", "pmcid": "PMC6222248", "primary_object": { "basename": "Arias_et_al-2018-Protein_Science.pdf", "url": "https://authors.library.caltech.edu/records/gc25g-j3s49/files/Arias_et_al-2018-Protein_Science.pdf" }, "resource_type": "article", "pub_year": "2018", "author_list": "Arias, Renee J.; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3we6s-w9529", "eprint_id": 79126, "eprint_status": "archive", "datestamp": "2023-08-21 21:50:22", "lastmod": "2023-10-26 14:36:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Segal-Helen-M", "name": { "family": "Segal", "given": "Helen M." } }, { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Hill-Michael-G", "name": { "family": "Hill", "given": "Michael G." } }, { "id": "Udit-Andrew-K", "name": { "family": "Udit", "given": "Andrew K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Electrochemical and Structural Characterization of Azotobacter vinelandii Flavodoxin II", "ispublished": "pub", "full_text_status": "public", "keywords": "Flavodoxin; Nitrogenase; X-ray Crystallography; Electrochemistry", "note": "\u00a9 2017 The Protein Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. \n\nReceived 1 June 2017; Accepted 10 July 2017. \n\nGrant sponsor: NIH grant (D.C.R.); Grant number: GM45162; Grant sponsor: NSF Grant (A.K.U.); Grant number: 1402029; Grant sponsor: Howard Hughes Medical Institute (D.C.R.). \n\nWe gratefully acknowledge discussions with Dr. James B. Howard, Dr. Jens Kaiser, Dr. Limei Zhang, Renee Arias, Christine Morrison and Belinda Wenke. We thank the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech, and the staff at Beamline 12\u20132, Stanford Synchrotron Radiation Lightsource (SSRL) for their assistance with data collection. SSRL is operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393) and the NCRR (P41RR001209). Coordinates and structure factors for wildtype Azotobacter vinelandii flavodoxin II have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics with ID 5K9B.\n\nPublished - PRO-26-1984.pdf
Supplemental Material - pro3236-sup-0001-SuppInfo.pdf
", "abstract": "Azotobacter vinelandii flavodoxin II serves as a physiological reductant of nitrogenase, the enzyme system mediating biological nitrogen fixation. Wildtype A. vinelandii flavodoxin II was electrochemically and crystallographically characterized to better understand the molecular basis for this functional role. The redox properties were monitored on surfactant-modified basal plane graphite electrodes, with two distinct redox couples measured by cyclic voltammetry corresponding to reduction potentials of \u2212483\u2009\u00b1\u20091 mV and \u2212187\u2009\u00b1\u20099 mV (vs. NHE) in 50 mM potassium phosphate, 150 mM NaCl, pH 7.5. These redox potentials were assigned as the semiquinone/hydroquinone couple and the quinone/semiquinone couple, respectively. This study constitutes one of the first applications of surfactant-modified basal plane graphite electrodes to characterize the redox properties of a flavodoxin, thus providing a novel electrochemical method to study this class of protein. The X-ray crystal structure of the flavodoxin purified from A. vinelandii was solved at 1.17 \u00c5 resolution. With this structure, the native nitrogenase electron transfer proteins have all been structurally characterized. Docking studies indicate that a common binding site surrounding the Fe-protein [4Fe:4S] cluster mediates complex formation with the redox partners Mo-Fe protein, ferredoxin I, and flavodoxin II. This model supports a mechanistic hypothesis that electron transfer reactions between the Fe-protein and its redox partners are mutually exclusive.", "date": "2017-10", "date_type": "published", "publication": "Protein Science", "volume": "26", "number": "10", "publisher": "Wiley", "pagerange": "1984-1993", "id_number": "CaltechAUTHORS:20170717-095833231", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170717-095833231", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NSF", "grant_number": "1402029" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" } ] }, "doi": "10.1002/pro.3236", "pmcid": "PMC5606536", "primary_object": { "basename": "PRO-26-1984.pdf", "url": "https://authors.library.caltech.edu/records/3we6s-w9529/files/PRO-26-1984.pdf" }, "related_objects": [ { "basename": "pro3236-sup-0001-SuppInfo.pdf", "url": "https://authors.library.caltech.edu/records/3we6s-w9529/files/pro3236-sup-0001-SuppInfo.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Segal, Helen M.; Spatzal, Thomas; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hp7kw-a4b81", "eprint_id": 78961, "eprint_status": "archive", "datestamp": "2023-08-19 04:37:36", "lastmod": "2023-10-23 15:05:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Morrison-Christine-M", "name": { "family": "Morrison", "given": "Christine N." }, "orcid": "0000-0002-4180-8407" }, { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Reversible Protonated Resting State of the Nitrogenase Active Site", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: June 1, 2017; Published: July 10, 2017. \n\nThis material is based upon work supported by the National Science Foundation Graduate Research Fellowship (Grant DGE-1144469 to C.N.M.), the National Institute of Health (NIH Grant GM45162 to D.C.R.), and the Howard Hughes Medical Institute (D.C.R.). \n\nWe acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech. We thank the staff at Beamline 12\u20132, Stanford Synchrotron Radiation Lightsource (SSRL), operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393), and the NCRR (P41RR001209). We thank Dr. Angelo Di Bilio for assisting with the EPR experiments, Dr. Lorenz Heidinger for providing a script for EPR simulations, Dr. Paul Oyala for assistance with the EPR simulations and analysis, and Dr. Jens Kaiser, Dr. James B. Howard, Dr. Kathryn Perez, Dr. Helen Segal, Belinda Wenke, and Renee Arias for helpful discussions. \n\nThe authors declare no competing financial interest.\n\n[Page 10862. The NSF grant supporting the Caltech EPR facility was inadvertently omitted from the Acknowledgments. The correct Acknowledgments is as follows, which\ndiffers from the originally published version through the addition of a last sentence \"The Caltech EPR Facility is supported by NSF-1531940.\"]\n\nOfficial citation:\nCorrection to Reversible Protonated Resting State of the Nitrogenase Active Site Christine N. Morrison, Thomas Spatzal, and Douglas C. Rees.\nJournal of the American Chemical Society 2017 139 (39), 13958-13958. DOI: 10.1021/jacs.7b09849.\n\nPublished - ja7b05695.pdf
Supplemental Material - ja7b05695_si_001.pdf
Erratum - jacs.7b09849.pdf
", "abstract": "Protonated states of the nitrogenase active site are mechanistically significant since substrate reduction is invariably accompanied by proton uptake. We report the low pH characterization by X-ray crystallography and EPR spectroscopy of the nitrogenase molybdenum iron (MoFe) proteins from two phylogenetically distinct nitrogenases (Azotobacter vinelandii, Av, and Clostridium pasteurianum, Cp) at pHs between 4.5 and 8. X-ray data at pHs of 4.5\u20136 reveal the repositioning of side chains along one side of the FeMo-cofactor, and the corresponding EPR data shows a new S = 3/2 spin system with spectral features similar to a state previously observed during catalytic turnover. The structural changes suggest that FeMo-cofactor belt sulfurs S3A or S5A are potential protonation sites. Notably, the observed structural and electronic low pH changes are correlated and reversible. The detailed structural rearrangements differ between the two MoFe proteins, which may reflect differences in potential protonation sites at the active site among nitrogenase species. These observations emphasize the benefits of investigating multiple nitrogenase species. Our experimental data suggest that reversible protonation of the resting state is likely occurring, and we term this state \"E_0H+\", following the Lowe\u2013Thorneley naming scheme.", "date": "2017-08-09", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "139", "number": "31", "publisher": "American Chemical Society", "pagerange": "10856-10862", "id_number": "CaltechAUTHORS:20170711-141051387", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170711-141051387", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" } ] }, "doi": "10.1021/jacs.7b05695", "pmcid": "PMC5553094", "primary_object": { "basename": "ja7b05695_si_001.pdf", "url": "https://authors.library.caltech.edu/records/hp7kw-a4b81/files/ja7b05695_si_001.pdf" }, "related_objects": [ { "basename": "jacs.7b09849.pdf", "url": "https://authors.library.caltech.edu/records/hp7kw-a4b81/files/jacs.7b09849.pdf" }, { "basename": "ja7b05695.pdf", "url": "https://authors.library.caltech.edu/records/hp7kw-a4b81/files/ja7b05695.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Morrison, Christine N.; Spatzal, Thomas; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/e2xqg-b3w93", "eprint_id": 84634, "eprint_status": "archive", "datestamp": "2023-08-19 03:58:43", "lastmod": "2023-10-18 16:25:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Site-specific X-ray Absorption Spectroscopy Study on Nitrogenase MoFe-protein", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2017 SBIC.", "abstract": "Nitrogenase is the only known biochemical machinery responsible for biological nitrogen fixation. In the process of biological nitrogen fixation, the nitrogenase MoFe-protein catalyzes the reduction of dinitrogen to ammonia at the FeMo-cofactor, upon receiving the electrons from the donor via Fe-protein. The two unusually large metalloclusters, the [7Fe:9S:Mo:C] FeMo\u2013cofactor and [8Fe:7S] P\u2013cluster, in the MoFe-protein highlight the richness of the redox chemistry available to nitrogenase for dinitrogen reduction. The information on the site-specific charge distribution within these metalloclusters is crucial towards ultimately understanding the mechanisms of nitrogenase at atomic-level. Multi-wavelength X-ray anomalous diffraction (MAD), by combining the strength of X-ray diffraction and X-ray absorption spectroscopy (XAS), provides a powerful tool for probing the local structure of the metals in a site-specific\nfashion. We have applied site-specific XAS to the MoFe-protein and other Fe-Sproteins as models for the study. The acquired site-specific Fe K-edge absorption spectra have been analyzed to assign relative oxidation states to irons in the\nmetalloclusters. The progress and challenges in this aspect of our work will be discussed. The results from the site-specific XAS studies on the MoFe-protein also demonstrate the presence of a mononuclear iron site, designated as Fe16, in addition to the fifteen iron sites present in the FeMo\u2013cofactor and P\u2013cluster. The Fe K-edge absorption data of the Fe16 site indicates that the iron is in the ferrous oxidation state. The high sequence conservation of the residues coordinated to Fe16 emphasizes the potential importance of the site in nitrogenase.", "date": "2017-07", "date_type": "published", "publication": "Journal of Biological Inorganic Chemistry", "volume": "22", "number": "S1", "publisher": "Springer", "pagerange": "S133", "id_number": "CaltechAUTHORS:20180201-143429975", "issn": "0949-8257", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180201-143429975", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1007/s00775-017-1475-y", "resource_type": "article", "pub_year": "2017", "author_list": "Zhang, Limei and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pd8ke-x1443", "eprint_id": 68690, "eprint_status": "archive", "datestamp": "2023-08-22 18:08:51", "lastmod": "2023-10-19 23:16:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bavi-Navid", "name": { "family": "Bavi", "given": "Navid" }, "orcid": "0000-0001-7040-0710" }, { "id": "Cortes-D-Marien", "name": { "family": "Cortes", "given": "D. Marien" } }, { "id": "Cox-Charles-D", "name": { "family": "Cox", "given": "Charles D." }, "orcid": "0000-0002-3802-6746" }, { "id": "Rohde-Paul-R", "name": { "family": "Rohde", "given": "Paul R." } }, { "id": "Liu-Weihong", "name": { "family": "Liu", "given": "Weihong" } }, { "id": "Deitmer-Jaochim-W", "name": { "family": "Deitmer", "given": "Joachim W." }, "orcid": "0000-0001-8763-7650" }, { "id": "Bavi-Omid", "name": { "family": "Bavi", "given": "Omid" }, "orcid": "0000-0003-3539-0849" }, { "id": "Strop-Pavel", "name": { "family": "Strop", "given": "Pavel" }, "orcid": "0000-0001-8695-577X" }, { "id": "Hill-Adam-P", "name": { "family": "Hill", "given": "Adam P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas" }, "orcid": "0000-0003-4073-1185" }, { "id": "Corry-Ben", "name": { "family": "Corry", "given": "Ben" }, "orcid": "0000-0002-6324-442X" }, { "id": "Perozo-Eduardo", "name": { "family": "Perozo", "given": "Eduardo" }, "orcid": "0000-0001-7132-2793" }, { "id": "Martinac-Boris", "name": { "family": "Martinac", "given": "Boris" }, "orcid": "0000-0001-8422-7082" } ] }, "title": "The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels", "ispublished": "pub", "full_text_status": "public", "keywords": "Biological sciences; Biophysics; Biochemistry", "note": "\u00a9 2016 Macmillan Publishers Limited, part of Springer Nature. \nThis work is licensed under a Creative Commons Attribution 4.0\nInternational License. The images or other third party material in this\narticle are included in the article's Creative Commons license, unless indicated otherwise\nin the credit line; if the material is not included under the Creative Commons license,\nusers will need to obtain permission from the license holder to reproduce the material.\nTo view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.\n\nReceived 24 December 2015. Accepted 18 May 2016. Published 22 June 2016.\n\nWe thank Dr Ulrike Schumann from the laboratory of Professor Ian R. Booth (Aberdeen University) for the construction and kind supply of the DE3 strain of MJF612.We also thank Dr Yoshitaka Nakayama, Dr Yousef Jamali, Professor Qing-hua Qin and Dr Chai-Ann Ng, for their useful suggestions and comments. Computational resources equipped with the commercial Abaqus/Standard software were provided by the National Computational Infrastructure (NCI) via the Merit Allocation and ANU Partner Schemes, supported by the\nAustralian Commonwealth Government. We also acknowledge the supercomputing facility at CSIRO. N.B. has been supported by a University International Postgraduate Award (UIPA) from the University of New South Wales. This project was supported by a grant and a Principal Research Fellowship to B.M. from the National Health and Medical Research Council of Australia. This work was also supported in part by funds from the Office of Health and Medical Research, NSW State Government and a grant from the NIH (GM063617).\n \n\nAuthor contributions:\nN.B., C.D.C, E.P., D.R., W.L. and B.M. designed research; N.B. and O.B. performed the\nsimulations. B.C. and A.P.H. helped and supported MD simulations. N.B., C.D.C., E.P.,\nM.D.C., P.S., J.W.D. and W.L performed the experiments; M.C., B.M. and E.P. carried\nout all the EPR-related experiments. P.R.R., N.B. and C.D.C. designed and carried out the\nmutagenesis and spheroplast formation. B.M., A.P.H., B.C., E.P. and D.R. contributed\nreagents/analytic tools; N.B., M.C., C.D.C., E.P., P.S. and B.M. analysed data; and N.B.,\nC.D.C., A.P.H., E.P. and B.M. wrote the manuscript. All authors read and approved the\nfinal manuscript.\n\nPublished - ncomms11984.pdf
Supplemental Material - ncomms11984-s1.pdf
Supplemental Material - ncomms11984-s2.avi
Supplemental Material - ncomms11984-s3.zip
", "abstract": "The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics.", "date": "2016-06-22", "date_type": "published", "publication": "Nature Communications", "volume": "7", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 11984", "id_number": "CaltechAUTHORS:20160627-123940721", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160627-123940721", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "University of New South Wales" }, { "agency": "National Health and Medical Research Council (NHMRC)" }, { "agency": "Office of Health and Medical Research (New South Wales)" }, { "agency": "NIH", "grant_number": "GM063617" } ] }, "doi": "10.1038/ncomms11984", "pmcid": "PMC4917966", "primary_object": { "basename": "ncomms11984-s1.pdf", "url": "https://authors.library.caltech.edu/records/pd8ke-x1443/files/ncomms11984-s1.pdf" }, "related_objects": [ { "basename": "ncomms11984-s2.avi", "url": "https://authors.library.caltech.edu/records/pd8ke-x1443/files/ncomms11984-s2.avi" }, { "basename": "ncomms11984-s3.zip", "url": "https://authors.library.caltech.edu/records/pd8ke-x1443/files/ncomms11984-s3.zip" }, { "basename": "ncomms11984.pdf", "url": "https://authors.library.caltech.edu/records/pd8ke-x1443/files/ncomms11984.pdf" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Bavi, Navid; Cortes, D. Marien; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tzbr1-7gc10", "eprint_id": 65564, "eprint_status": "archive", "datestamp": "2023-08-20 10:53:46", "lastmod": "2023-10-18 16:08:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Schlesier-Julia", "name": { "family": "Schlesier", "given": "Julia" } }, { "id": "Burger-Eva-Maria", "name": { "family": "Burger", "given": "Eva-Maria" } }, { "id": "Sippel-Daniel", "name": { "family": "Sippel", "given": "Daniel" } }, { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Andrade-Susana-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Einsle-Oliver", "name": { "family": "Einsle", "given": "Oliver" }, "orcid": "0000-0001-8722-2893" } ] }, "title": "Nitrogenase FeMoco investigated by spatially resolved anomalous dispersion refinement", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2016 Nature Publishing Group. \nThis work is licensed under a Creative Commons Attribution 4.0\nInternational License. The images or other third party material in this\narticle are included in the article's Creative Commons license, unless indicated otherwise\nin the credit line; if the material is not included under the Creative Commons license,\nusers will need to obtain permission from the license holder to reproduce the material.\nTo view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.\n\nReceived 25 Aug 2015. Accepted 31 Jan 2016. Published 14 Mar 2016.\n\nWe thank Serena DeBeer for stimulating and helpful discussions and the staff at the Swiss Light Source, Villigen, CH, and the Stanford Synchrotron Radiation Laboratory, Palo Alto, CA, USA, for assistance during data collection. We acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute at Caltech for their generous support of the Molecular Observatory at Caltech. This work was supported by the Deutsche Forschungsgemeinschaft (RTG 1976 to S.L.A. and O.E. and EI 520/7 to O.E.) and the European Research Council (grant 310656 to O.E.), NIH (grant GM45162 to D.C.R.) and an NSERC PDF award (L.M.Z.).\n\nAuthor contributions:\nT.S., S.L.A., D.C.R. and O.E. designed the experiments; T.S., J.S. and E.-M.B. performed\nthe experiments; T.S., L.Z., D.S., S.L.A., D.C.R. and O.E. analysed the data; T.S., S.L.A.\nand O.E. wrote the paper.\n\nCompeting financial interests: \nThe authors declare no competing financial interests.\n\nPublished - ncomms10902.pdf
Supplemental Material - ncomms10902-s1.pdf
", "abstract": "The [Mo:7Fe:9S:C] iron-molybdenum cofactor (FeMoco) of nitrogenase is the largest known metal cluster and catalyses the 6-electron reduction of dinitrogen to ammonium in biological nitrogen fixation. Only recently its atomic structure was clarified, while its reactivity and electronic structure remain under debate. Here we show that for its resting S=3/2 state the common iron oxidation state assignments must be reconsidered. By a spatially resolved refinement of the anomalous scattering contributions of the 7 Fe atoms of FeMoco, we conclude that three irons (Fe1/3/7) are more reduced than the other four (Fe2/4/5/6). Our data are in agreement with the recently revised oxidation state assignment for the molybdenum ion, providing the first spatially resolved picture of the resting-state electron distribution within FeMoco. This might provide the long-sought experimental basis for a generally accepted theoretical description of the cluster that is in line with available spectroscopic and functional data.", "date": "2016-03-14", "date_type": "published", "publication": "Nature Communications", "volume": "7", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 10902", "id_number": "CaltechAUTHORS:20160322-065458303", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160322-065458303", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "RTG 1976" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "EI 520/7" }, { "agency": "European Research Council (ERC)", "grant_number": "310656" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" } ] }, "doi": "10.1038/ncomms10902", "pmcid": "PMC4793075", "primary_object": { "basename": "ncomms10902-s1.pdf", "url": "https://authors.library.caltech.edu/records/tzbr1-7gc10/files/ncomms10902-s1.pdf" }, "related_objects": [ { "basename": "ncomms10902.pdf", "url": "https://authors.library.caltech.edu/records/tzbr1-7gc10/files/ncomms10902.pdf" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Spatzal, Thomas; Schlesier, Julia; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/03jaz-3eb25", "eprint_id": 67670, "eprint_status": "archive", "datestamp": "2023-08-20 10:22:05", "lastmod": "2023-10-18 21:22:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yang-Janet-G", "name": { "family": "Yang", "given": "Janet G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Allosteric Regulatory Mechanism of the E.Coli Metni Methionine ABC Transporter", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2016 Biophysical Society. Published by Elsevier Inc.", "abstract": "The MetNI methionine importer of Escherichia coli, an ATP Binding Cassette (ABC) transporter, uses the energy of ATP binding and hydrolysis to catalyze the high affinity uptake of D- and L-methionine. Early in vivo studies showed that the uptake of external methionine is repressed by the level of the internal methionine pool, a phenomenon termed transinhibition. Our understanding of MetNI mechanism has thus far been limited to a series of crystal structures in an inward facing conformation. To understand the molecular mechanism of transinhibition, we studied the kinetics of ATP hydrolysis using detergent-solubilized MetNI. We find that transinhibition is due to noncompetitive inhibition by L-methionine, much like a negative feedback loop. Thermodynamic analyses revealed two allosteric methionine binding sites per transporter. This quantitative analysis of transinhibition, the first to our knowledge for a structurally defined transporter, builds upon the previously proposed structurally based model for regulation. This mechanism of regulation at the transporter activity level could be applicable to not only ABC transporters but other types of membrane transporters as well.", "date": "2016-02-16", "date_type": "published", "publication": "Biophysical Journal", "volume": "110", "number": "3", "publisher": "Biophysical Society", "pagerange": "140A", "id_number": "CaltechAUTHORS:20160606-075431894", "issn": "0006-3495", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160606-075431894", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/j.bpj.2015.11.796", "resource_type": "article", "pub_year": "2016", "author_list": "Yang, Janet G. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/63k6v-q4457", "eprint_id": 63112, "eprint_status": "archive", "datestamp": "2023-08-20 09:29:57", "lastmod": "2023-10-25 23:33:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Spatzal-T", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Perez-K-A", "name": { "family": "Perez", "given": "Kathryn A." } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015, Spatzal et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. \n\nReceived September 15, 2015. Accepted December 15, 2015. Published December 16, 2015. \n\nWe thank J. Rittle, J.C. Peters, B. Wenke, H. Segal, C. Morrison and O. Einsle for informative discussions. This work was supported by NIH grant GM45162 (D.C.R.). We gratefully acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi\u2013Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech, and the staff at Beamline 12\u20132, Stanford Synchrotron Radiation Lightsource (SSRL) for their assistance with data collection. SSRL is operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393) and the NCRR (P41RR001209). We thank the Center for Environmental Microbial Interactions and the William T. Gimbel Discovery fund for their support of microbiology research at Caltech. \n\nThese authors contributed equally to this work: Thomas Spatzal, Kathryn A Perez. \n\nAuthor contributions: TS, Purified, crystallized and biochemically characterized the enzyme samples, and collected the X-ray crystallographic data; Processed, refined and analyzed the X-ray data; Contributed equally to the study; Discussed the results and participated in writing the manuscript; Initiated and directed this research. KAP, Purified, crystallized and biochemically characterized the enzyme samples, and collected the X-ray crystallographic data; Processed, refined and analyzed the X-ray data; Contributed equally to the study; Discussed the results and participated in writing the manuscript. JBH, Contributed to the experimental design and data interpretation; Discussed the results and participated in writing the manuscript. DCR, Discussed the results and participated in writing the manuscript; Initiated and directed this research, Conception and design, Analysis and interpretation of data, Drafting or revising the article. \n\nThe authors declare that no competing interests exist. \n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. \n\nReviewing editor: Wilfred A van der Donk, Reviewing editor, University of Illinois at Urbana-Champaign, United States\n\nPublished - elife-11620-v2-download.pdf
", "abstract": "Dinitrogen reduction in the biological nitrogen cycle is catalyzed by nitrogenase, a two-component metalloenzyme. Understanding of the transformation of the inert resting state of the active site FeMo-cofactor into an activated state capable of reducing dinitrogen remains elusive. Here we report the catalysis dependent, site-selective incorporation of selenium into the FeMo-cofactor from selenocyanate as a newly identified substrate and inhibitor. The 1.60 \u00c5 resolution structure reveals selenium occupying the S2B site of FeMo-cofactor in the Azotobacter vinelandii MoFe-protein, a position that was recently identified as the CO-binding site. The Se2B-labeled enzyme retains substrate reduction activity and marks the starting point for a crystallographic pulse-chase experiment of the active site during turnover. Through a series of crystal structures obtained at resolutions of 1.32-1.66 \u00c5, including the CO-inhibited form of Av1-Se2B, the exchangeability of all three belt-sulfur sites is demonstrated, providing direct insights into unforeseen rearrangements of the metal center during catalysis.", "date": "2015-12-16", "date_type": "published", "publication": "eLife", "volume": "4", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e11620", "id_number": "CaltechAUTHORS:20151221-153134644", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151221-153134644", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Sanofi\u2013Aventis Bioengineering Research Program" }, { "agency": "National Institute of General Medical Sciences (NIGMS)", "grant_number": "P41GM103393" }, { "agency": "National Center for Research Resources (NCRR)", "grant_number": "P41RR001209" }, { "agency": "Department of Energy (DOE)" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" } ] }, "doi": "10.7554/eLife.11620", "pmcid": "PMC4755756", "primary_object": { "basename": "elife-11620-v2-download.pdf", "url": "https://authors.library.caltech.edu/records/63k6v-q4457/files/elife-11620-v2-download.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Spatzal, Thomas; Perez, Kathryn A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0j56f-nez29", "eprint_id": 60068, "eprint_status": "archive", "datestamp": "2023-08-22 16:14:36", "lastmod": "2023-10-24 14:51:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Nguyen-Phong-T", "name": { "family": "Nguyen", "given": "Phong T." } }, { "id": "Li-Qi-Wen", "name": { "family": "Li", "given": "Qi Wen" } }, { "id": "Kadaba-Neena-S", "name": { "family": "Kadaba", "given": "Neena S." } }, { "id": "Lai-Jeffrey-Y", "name": { "family": "Lai", "given": "Jeffrey Y." }, "orcid": "0000-0003-2863-4411" }, { "id": "Yang-Janet-G", "name": { "family": "Yang", "given": "Janet G." }, "orcid": "0000-0002-5619-9544" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The contribution of methionine to the stability of the Escherichia coli MetNIQ ABC transporter-substrate binding protein complex", "ispublished": "pub", "full_text_status": "public", "keywords": "ABC transporter; methionine-binding protein; methionine transporter; MetNI, MetQ; L-methionine; transinhibition", "note": "\u00a9 2015 De Gruyter. \n\nReceived February 18, 2015; accepted March 19, 2015; previously published online March 23, 2015. \n\nA Vietnam International Education Development scholarship from the Vietnam Ministry of Education and Training scholarship to P.T.N, an NSF Graduate Fellowship to Q.W.L., and support of NIH Predoctoral Training Grant T32 GM07737 to N.S.K., are gratefully acknowledged. We thank Allen Lee for generating the original MetNIQ constructs, Christoph M\u00fcller for MetNIQ discussions, and Dr. Jens Kaiser and Dr. Nathan Dalleska for assistance with crystallography and ICP-MS, respectively. We gratefully acknowledge the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech and the staff at Beamline 12\u20132, Stanford Synchrotron Radiation Lightsource (SSRL), for their assistance with data collection. Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). This project benefited from the use of instrumentation made available by the Caltech Environmental Analysis Center. This work was supported in part by NIH grant GM045162.\n\nPublished - Nguyen_2015p1127.pdf
Accepted Version - nihms729241.pdf
", "abstract": "Despite the ubiquitous role of ATP-binding cassette (ABC) importers in nutrient uptake, only the Escherichia coli maltose and vitamin B_(12) ABC transporters have been structurally characterized in multiple conformations relevant to the alternating access transport mechanism. To complement our previous structure determination of the E. coli MetNI methionine importer in the inward facing conformation (Kadaba et al. (2008) Science 321, 250-253), we have explored conditions stabilizing the outward facing conformation. Using two variants, the Walker B E166Q mutation with ATP+EDTA to stabilize MetNI in the ATPbound conformation and the N229A variant of the binding protein MetQ, shown in this work to disrupt methionine binding, a high affinity MetNIQ complex was formed with a dissociation constant measured to be 27 nm. Using wild type MetQ containing a co-purified methionine (for which the crystal structure is reported at 1.6 \u00c5 resolution), the dissociation constant for complex formation with MetNI is measured to be ~40-fold weaker, indicating that complex formation lowers the affinity of MetQ for methionine by this amount. Preparation of a stable MetNIQ complex is an essential step towards the crystallographic analysis of the outward facing conformation, a key intermediate in the uptake of methionine by this transport system.", "date": "2015-09", "date_type": "published", "publication": "Biological Chemistry", "volume": "396", "number": "9-10", "publisher": "De Gruyter", "pagerange": "1127-1134", "id_number": "CaltechAUTHORS:20150904-082226280", "issn": "1431-6730", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150904-082226280", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32 GM07737" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-76SF00515" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1515/hsz-2015-0131", "pmcid": "PMC4621241", "primary_object": { "basename": "Nguyen_2015p1127.pdf", "url": "https://authors.library.caltech.edu/records/0j56f-nez29/files/Nguyen_2015p1127.pdf" }, "related_objects": [ { "basename": "nihms729241.pdf", "url": "https://authors.library.caltech.edu/records/0j56f-nez29/files/nihms729241.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Nguyen, Phong T.; Li, Qi Wen; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jrwba-8qn12", "eprint_id": 57630, "eprint_status": "archive", "datestamp": "2023-09-22 22:29:31", "lastmod": "2023-10-23 23:23:09", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Mattle-D", "name": { "family": "Mattle", "given": "Daniel" } }, { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Sitsel-O", "name": { "family": "Sitsel", "given": "Oleg" } }, { "id": "Pedersen-L-T", "name": { "family": "Pedersen", "given": "Lotte Thue" } }, { "id": "Moncelli-M-R", "name": { "family": "Moncelli", "given": "Maria Rosa" } }, { "id": "Tadini-Buoninsegni-F", "name": { "family": "Tadini-Buoninsegni", "given": "Francesco" } }, { "id": "Gourdon-P", "name": { "family": "Gourdon", "given": "Pontus" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Nissen-P-E", "name": { "family": "Nissen", "given": "Poul" } }, { "id": "Meloni-G", "name": { "family": "Meloni", "given": "Gabriele" } } ] }, "title": "A sulfur-based transport pathway in Cu^+-ATPases", "ispublished": "pub", "full_text_status": "public", "keywords": "charge transfer measurements; Cu+ coordination; Cu+-ATPase; membrane protein transporter; P-type ATPase; X-ray absorption spectroscopy", "note": "\u00a9 2015 The Authors. Received 26 November 2014; Revised 13 March 2015; Accepted 31 March 2015. Published online 08.05.2015.\n\nD.M. was supported by an EMBO Short\u2010Term Fellowship (ASTF\u201011\u20102012) and the Graduate School of Science and Technology, Aarhus University. G.M. was supported by a Marie Curie International Outgoing Fellowship (European Commission, grant no. 252961). L.Z. was supported by an NSERC Postdoctoral Fellowship. Work at Caltech was supported by NIH grant GM45162 to D.C.R. We thank Prof. G.N. George (University of Saskatchewan, Canada), Prof. D. Winge (University of Utah, USA), and Prof. D.P. Giedroc (University of Indiana, USA) for providing the XANES spectra of model compounds, Cox17 and MtCsoR, respectively. We thank the staff at Beamline 7\u20133, Stanford Synchrotron Radiation Lightsource (SSRL). SSRL is operated for the DOE and supported by OBER and by the NIH, NIGMS (P41GM103393), and the NCRR (P41RR001209). M.R.M. and F.T.\u2010B. gratefully acknowledge financial support from the Ente Cassa di Risparmio di Firenze and the Italian Ministry of University and Research (PON01_00937). P.N. was supported by the BIOMEMOS advanced research grant of the European Research Council (250322). This project benefited from discussion with Nathan Dalleska and instrumentation made available by the Caltech Environmental Analysis Center.\n\nAuthor contributions\nDM and GM designed the experiments assisted by DCR, PG, and PN. Mutant\nconstructs were generated by DM and LTP and DM and GM purified the\nprotein samples. GM and LZ recorded the XAS data and analyzed the data\ntogether with DM; DM and GM performed and analyzed the stoichiometry\nexperiments; DM and GM performed and analyzed the ATPase activity experiments.\nOS prepared membranes for charge transfer measurements. FT-B and\nMRM designed and performed concentration jump experiments on solidsupported\nmembrane; FT-B analyzed and summarized charge transfer\nmeasurements. DM and GM summarized the results and prepared the manuscript\nfigures, and DM, GM, and PN wrote the paper with comments from all\nauthors. DCR, PG, and PN supervised the work.\n\nSupplemental Material - inline-supplementary-material-1.pdf
", "abstract": "Cells regulate copper levels tightly to balance the biogenesis and integrity of copper centers in vital enzymes against toxic levels of copper. P_(IB)\u2010type Cu^+\u2010ATPases play a central role in copper homeostasis by catalyzing the selective translocation of Cu^+ across cellular membranes. Crystal structures of a copper\u2010free Cu^+\u2010ATPase are available, but the mechanism of Cu^+ recognition, binding, and translocation remains elusive. Through X\u2010ray absorption spectroscopy, ATPase activity assays, and charge transfer measurements on solid\u2010supported membranes using wild\u2010type and mutant forms of the Legionella pneumophila Cu^+\u2010ATPase (LpCopA), we identify a sulfur\u2010lined metal transport pathway. Structural analysis indicates that Cu^+ is bound at a high\u2010affinity transmembrane\u2010binding site in a trigonal\u2010planar coordination with the Cys residues of the conserved CPC motif of transmembrane segment 4 (C382 and C384) and the conserved Met residue of transmembrane segment 6 (M717 of the MXXXS motif). These residues are also essential for transport. Additionally, the studies indicate essential roles of other conserved intramembranous polar residues in facilitating copper binding to the high\u2010affinity site and subsequent release through the exit pathway.", "date": "2015-06-01", "date_type": "published", "publication": "EMBO Reports", "volume": "16", "number": "6", "publisher": "European Molecular Biology Organization", "pagerange": "728-740", "id_number": "CaltechAUTHORS:20150519-074158936", "issn": "1469-221X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150519-074158936", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "European Molecular Biology Organization (EMBO)", "grant_number": "ASTF\u201011\u20102012" }, { "agency": "Aarhus University" }, { "agency": "Marie Curie Fellowship", "grant_number": "252961" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "OBER" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "Ente Cassa di Risparmio di Firenze" }, { "agency": "Ministero dell'Istruzione, dell'Universit\u00e0 e della Ricerca (MIUR)", "grant_number": "PON01_00937" }, { "agency": "European Research Council (ERC)", "grant_number": "250322 Biomemos" } ] }, "doi": "10.15252/embr.201439927", "pmcid": "PMC4467857", "primary_object": { "basename": "inline-supplementary-material-1.pdf", "url": "https://authors.library.caltech.edu/records/jrwba-8qn12/files/inline-supplementary-material-1.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Mattle, Daniel; Zhang, Limei; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4a7mq-b3325", "eprint_id": 46075, "eprint_status": "archive", "datestamp": "2023-08-20 06:25:31", "lastmod": "2023-10-26 18:40:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Walton-T-A", "name": { "family": "Walton", "given": "Troy A." } }, { "id": "Idigo-C-A", "name": { "family": "Idigo", "given": "Chinenye A." } }, { "id": "Herrera-N", "name": { "family": "Herrera", "given": "Nadia" }, "orcid": "0000-0003-4157-9429" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "MscL: channeling membrane tension", "ispublished": "pub", "full_text_status": "public", "keywords": "Mechanosensitive channels. Stretch activated channels. Bacterial channels. Hypo-osmotic stress response. \nTurgor pressure", "note": "\u00a9 2014 Springer-Verlag Berlin Heidelberg. \n\nReceived: 7 April 2014. Revised: 6 May 2014. Accepted: 9 May 2014. \n\nWe thank Chris Gandhi, Rob Phillips, Elizabeth Haswell, and Ian Booth for stimulating discussions. N. Herrera is the recipient of a Gilliam graduate fellowship of the Howard Hughes Medical Institute, and C. Idigo received support from the US National Institutes of Health/National Research Service Award T32 GM07616. Research in the authors' lab was supported by US National Institutes of Health grant GM84211.\n\nAccepted Version - nihms599119.pdf
", "abstract": "Mechanosensitive channels are integral components for the response of bacteria to osmotic shock. The mechanosensitive channel of large conductance (MscL) responds to extreme turgor pressure increase that would otherwise lyse the cellular membrane. MscL has been studied as a model mechanosensitive channel using both structural and functional approaches. We will summarize the structural data and discuss outstanding questions surrounding the gating mechanism of this homo-oligomeric channel that has ~3 nS conductance. Specifically, we will explore the following: (1) the variability in oligomeric state that has been observed, (2) the open pore size measurements, and (3) the role of the C-terminal coiled coil domain for channel function. The oligomeric state of MscL has been characterized using various techniques, with a pentamer being the predominant form; however, the presence of mixtures of oligomers in the membrane is still uncertain. In the absence of structural data for the open state of MscL, the diameter of the open state pore has been estimated by several different approaches, leading to a current estimate between 25 and 30 \u00c5. While the C-terminal domain is highly conserved among MscL homologues, it is not required for activity in vivo or in vitro. This domain is likely to remain intact during the gating transition and perform a filtering function that retains valuable osmolytes in the cytosol. Overall, studies of MscL have provided significant insight to the field, and serve as a paradigm for the analysis of non-homologous, eukaryotic mechanosensitive channel proteins.", "date": "2015-06", "date_type": "published", "publication": "Pfl\u00fcgers Archiv European Journal of Physiology", "volume": "467", "number": "1", "publisher": "Springer", "pagerange": "15-25", "id_number": "CaltechAUTHORS:20140604-130904300", "issn": "0031-6768", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140604-130904300", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32 GM076165" }, { "agency": "NIH", "grant_number": "GM84211" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1007/s00424-014-1535-x", "pmcid": "PMC4246047", "primary_object": { "basename": "nihms599119.pdf", "url": "https://authors.library.caltech.edu/records/4a7mq-b3325/files/nihms599119.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Walton, Troy A.; Idigo, Chinenye A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/dhg9z-7k792", "eprint_id": 58380, "eprint_status": "archive", "datestamp": "2023-08-20 06:21:25", "lastmod": "2023-10-23 19:17:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Reading-Eamonn", "name": { "family": "Reading", "given": "Eamonn" } }, { "id": "Walton-Troy-A", "name": { "family": "Walton", "given": "Troy A." } }, { "id": "Liko-Idir", "name": { "family": "Liko", "given": "Idlir" } }, { "id": "Marty-Michael-T", "name": { "family": "Marty", "given": "Michael T." } }, { "id": "Laganowsky-Arthur", "name": { "family": "Laganowsky", "given": "Arthur" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Robinson-Carol-V", "name": { "family": "Robinson", "given": "Carol V." } } ] }, "title": "The Effect of Detergent, Temperature, and Lipid on the Oligomeric State of MscL Constructs: Insights from Mass Spectrometry", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Elsevier Ltd.\n\nReceived: March 11, 2015; Revised: April 23, 2015; Accepted: April 27, 2015; Published: May 21, 2015. \n\nThis work was supported by an ERC Advanced Investigator Award (26851) (IMPRESS), a Royal Society Research Professorship, a Medical Research Council Program Grant (98101) and an NIH grant GM084211.\n\nAuthor Contributions: E.R., T.A.W., I.L., and A.L. performed the experiments and analyzed the data. E.R., T.A.W., A.L., D.C.R, and C.V.R designed the study. M.T.M. developed the deconvolution software and provided analysis support for this study. E.R. and C.V.R. wrote the article with contributions from all other authors. \n\nSupplemental Information includes three tables and ten figures and can\nbe found with this article online at http://dx.doi.org/10.1016/j.chembiol.2015.04.016.\n\nAccepted Version - nihms-1028275.pdf
Supplemental Material - mmc1.pdf
", "abstract": "The mechanosensitive channel of large conductance (MscL) acts as an emergency release valve for osmotic shock of bacteria preventing cell lysis. The large pore size, essential for function, requires the formation of oligomers with tetramers, pentamers, or hexamers observed depending on the species and experimental approach. We applied non-denaturing (native) mass spectrometry to five different homologs of MscL to determine the oligomeric state under more than 50 different experimental conditions elucidating lipid binding and subunit stoichiometry. We found equilibrium between pentameric and tetrameric species, which can be altered by detergent, disrupted by binding specific lipids, and perturbed by increasing temperature (37\u00b0C). We also established the presence of lipopolysaccharide bound to MscL and other membrane proteins expressed in Escherichia coli, revealing a potential source of heterogeneity. More generally, we highlight the use of mass spectrometry in probing membrane proteins under a variety of detergent-lipid environments relevant to structural biology.", "date": "2015-05-21", "date_type": "published", "publication": "Chemistry and Biology", "volume": "22", "number": "5", "publisher": "Cell Press", "pagerange": "593-603", "id_number": "CaltechAUTHORS:20150619-104444107", "issn": "1074-5521", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150619-104444107", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "European Research Council", "grant_number": "26851" }, { "agency": "Royal Society" }, { "agency": "Medical Research Council", "grant_number": "98101" }, { "agency": "NIH", "grant_number": "GM084211" } ] }, "doi": "10.1016/j.chembiol.2015.04.016", "pmcid": "PMC6585436", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/dhg9z-7k792/files/mmc1.pdf" }, "related_objects": [ { "basename": "nihms-1028275.pdf", "url": "https://authors.library.caltech.edu/records/dhg9z-7k792/files/nihms-1028275.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Reading, Eamonn; Walton, Troy A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/31m00-gp461", "eprint_id": 55090, "eprint_status": "archive", "datestamp": "2023-08-20 05:44:59", "lastmod": "2023-10-20 21:20:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yang-Janet-G", "name": { "family": "Yang", "given": "Janet G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Allosteric Regulatory Mechanism of the Escherichia coli MetNI Methionine ATP Binding Cassette (ABC) Transporter", "ispublished": "pub", "full_text_status": "public", "keywords": "ABC transporter, amino acid transport, ATPase, enzyme mechanism, methionine", "note": "\u00a9 2015 by The American Society for Biochemistry and Molecular Biology, Inc. \n\nReceived August 7, 2014, Accepted February 12, 2015, First Published on February 12, 2015. \n\nWe thank Eric Johnson and Chris Vercollone for early initial studies, Kana Takematsu for discussion regarding modeling, and Jeff Lai for technical assistance. \n\nThis work was supported by NIH Grant R01 GM45162 to DCR.\n\nPublished - 9135.full.pdf
Supplemental Material - jbc.M114.603365-1.pdf
", "abstract": "The MetNI methionine importer of Escherichia coli, an ATP Binding Cassette (ABC) transporter, uses the energy of ATP binding and hydrolysis to catalyze the high affinity uptake of D- and L-methionine. Early in vivo studies showed that the uptake of external methionine is repressed by the level of the internal methionine pool, a phenomenon termed transinhibition. Our understanding of MetNI mechanism has thus far been limited to a series of crystal structures in an inward facing conformation. To understand the molecular mechanism of transinhibition, we studied the kinetics of ATP hydrolysis using detergent-solubilized MetNI. We find that transinhibition is due to noncompetitive inhibition by L-methionine, much like a negative feedback loop. Thermodynamic analyses revealed two allosteric methionine binding sites per transporter. This quantitative analysis of transinhibition, the first to our knowledge for a structurally defined transporter, builds upon the previously proposed structurally based model for regulation. This mechanism of regulation at the transporter activity level could be applicable to not only ABC transporters but other types of membrane transporters as well.", "date": "2015-04-03", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "290", "number": "14", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "9135-9140", "id_number": "CaltechAUTHORS:20150223-091438070", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150223-091438070", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM45162" } ] }, "doi": "10.1074/jbc.M114.603365", "pmcid": "PMC4423698", "primary_object": { "basename": "9135.full.pdf", "url": "https://authors.library.caltech.edu/records/31m00-gp461/files/9135.full.pdf" }, "related_objects": [ { "basename": "jbc.M114.603365-1.pdf", "url": "https://authors.library.caltech.edu/records/31m00-gp461/files/jbc.M114.603365-1.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Yang, Janet G. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/znamd-azn23", "eprint_id": 55843, "eprint_status": "archive", "datestamp": "2023-08-20 05:31:27", "lastmod": "2023-10-20 23:17:42", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Morrison-C-N", "name": { "family": "Morrison", "given": "Christine N." }, "orcid": "0000-0002-4180-8407" }, { "id": "Hoy-J-A", "name": { "family": "Hoy", "given": "Julie A." } }, { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Substrate Pathways in the Nitrogenase MoFe Protein by Experimental Identification of Small Molecule Binding Sites", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: October 20, 2014. Revised: February 18, 2015. Publication Date (Web): February 24, 2015.\n\nFunding: This material is based upon work supported by the National Science Foundation Graduate Research Fellowship (Grant DGE-1144469 to C.N.M.), the National Institute of Health (NIH Grant GM45162 to D.C.R.), the Howard Hughes Medical Institute (to D.C.R.), the European Research Council (Grant 310656 to O. E.), and Deutsche Forschungsgemeinschaft (Grants Ei-520/7 and IRTG 1478 to O.E.).\n\nWe acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech. We thank the staff at Beamline 12-2, Stanford Synchrotron Radiation Lightsource (SSRL), operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393), and the NCRR (P41RR001209). We thank Jens Kaiser and James Howard for helpful discussions as well as Thomas Spatzal for discussions and his assistance with the xenon pressurization. \n\nAccession Codes: The structural model and structure factors have been deposited with the Protein Data Bank. The PDB ID for the Av1-Xe and Cp1-Xe structures are 4WNA and 4WN9, respectively.\n\nPublished - bi501313k.pdf
Supplemental Material - bi501313k_si_001.pdf
Supplemental Material - bi501313k_si_002.mpg
", "abstract": "In the nitrogenase molybdenum-iron (MoFe) protein, we have identified five potential substrate access pathways from the protein surface to the FeMo-cofactor (the active site) or the P-cluster using experimental structures of Xe pressurized into MoFe protein crystals from Azotobacter vinelandii and Clostridium pasteurianum. Additionally, all published structures of the MoFe protein, including those from Klebsiella pneumoniae, were analyzed for the presence of nonwater, small molecules bound to the protein interior. Each pathway is based on identification of plausible routes from buried small molecule binding sites to both the protein surface and a metallocluster. Of these five pathways, two have been previously suggested as substrate access pathways. While the small molecule binding sites are not conserved among the three species of MoFe protein, residues lining the pathways are generally conserved, indicating that the proposed pathways may be accessible in all three species. These observations imply that there is unlikely a unique pathway utilized for substrate access from the protein surface to the active site; however, there may be preferred pathways such as those described here.", "date": "2015-03-24", "date_type": "published", "publication": "Biochemistry", "volume": "54", "number": "11", "publisher": "American Chemical Society", "pagerange": "2052-2060", "id_number": "CaltechAUTHORS:20150317-100736214", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150317-100736214", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "European Research Council (ERC)", "grant_number": "310656" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "Ei-520/7" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "IRTG 1478" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Caltech Sanofi-Aventis Bioengineering Research Program" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" } ] }, "doi": "10.1021/bi501313k", "pmcid": "PMC4590346", "primary_object": { "basename": "bi501313k.pdf", "url": "https://authors.library.caltech.edu/records/znamd-azn23/files/bi501313k.pdf" }, "related_objects": [ { "basename": "bi501313k_si_001.pdf", "url": "https://authors.library.caltech.edu/records/znamd-azn23/files/bi501313k_si_001.pdf" }, { "basename": "bi501313k_si_002.mpg", "url": "https://authors.library.caltech.edu/records/znamd-azn23/files/bi501313k_si_002.mpg" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Morrison, Christine N.; Hoy, Julie A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4pbfa-xzb90", "eprint_id": 56711, "eprint_status": "archive", "datestamp": "2023-08-20 05:21:38", "lastmod": "2023-10-23 15:44:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Cotton Medal to Douglas Rees", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2015 American Chemical Society.", "abstract": "Douglas C. Rees, Roscoe Gilkey Dickinson\nProfessor of Chemistry at California Institute\nof Technology and a Howard Hughes\nMedical Institute investigator, is the winner\nof the F. A. Cotton Medal for Excellence\nin Chemical Research,\nsponsored by the ACS\nTexas A&M University\nSection and the Texas\nA&M department of\nchemistry.", "date": "2015-03-09", "date_type": "published", "publication": "Chemical and Engineering News", "volume": "93", "number": "10", "publisher": "American Chemical Society", "pagerange": "49", "id_number": "CaltechAUTHORS:20150416-093349159", "issn": "0009-2347", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150416-093349159", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "resource_type": "article", "pub_year": "2015", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ss1jy-j6526", "eprint_id": 58902, "eprint_status": "archive", "datestamp": "2023-08-20 05:15:06", "lastmod": "2023-10-23 19:51:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Powering brain power: GLUT1 and the era of structure based human transporter biology", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Oxford University Press.\n\nReceived November 22, 2014. \nAccepted November 28, 2014.\nFirst published online: December 8, 2014.\n\nAccepted Version - nihms670550.pdf
", "abstract": "Every student of biochemistry quickly appreciates\nthe central role of glycolysis\nin cellular metabolism. What is not usually\naddressed in an introductory course\nis how glucose gets inside a cell in the\nfirst place. Specialized integral membrane\nproteins known as transporters are responsible\nfor glucose uptake; in mammals,\nglucose is imported by members of\nthe GLUT family of which 14 different\nvarieties have been identified in humans\n[1]. GLUT transporters are members of\nthe major facilitator superfamily of transporters\nand catalyze the facilitated uptake\nof glucose in the thermodynamically\nfavored direction. The most widely distributed\nversion isGLUT1that is responsible\nfor getting glucose into red blood\ncells and across the blood brain barrier,\namong many other roles [2].", "date": "2015-03", "date_type": "published", "publication": "National Science Review", "volume": "2", "number": "1", "publisher": "Oxford University Press", "pagerange": "3-4", "id_number": "CaltechAUTHORS:20150716-080222139", "issn": "2095-5138", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150716-080222139", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1093/nsr/nwu075", "pmcid": "PMC4411962", "primary_object": { "basename": "nihms670550.pdf", "url": "https://authors.library.caltech.edu/records/ss1jy-j6526/files/nihms670550.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k34wx-08z71", "eprint_id": 55664, "eprint_status": "archive", "datestamp": "2023-08-20 04:45:52", "lastmod": "2023-10-20 22:56:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Li-Mei" } }, { "id": "Morrison-C-N", "name": { "family": "Morrison", "given": "Christine N." }, "orcid": "0000-0002-4180-8407" }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase MoFe protein from Clostridium pasteurianum at 1.08 \u00c5 resolution: comparison with the Azotobacter vinelandii MoFe protein", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 International Union of Crystallography. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. \n\nReceived 27 October 2014; Accepted 17 November 2014.\n\nWe thank Dr J. B. Howard for contributions to this project. The work was supported by NIH grant GM45162 to DCR, a National Sciences and Engineering Research Council of Canada postdoctoral fellowship and Caltech Center for Environmental Microbial Interactions fellowships to L-MZ and a National Science Foundation Graduate Research Fellowship (grant DGE-1144469 to CNM). We thank the staff at beamline 12-2, Stanford Synchrotron Radiation Lightsource (SSRL) for their assistance. SSRL is operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393) and the NCRR (P41RR001209). We acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute and the Sanofi\u2013Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech.\n\nPublished - lp5003.pdf
", "abstract": "The X-ray crystal structure of the nitrogenase MoFe protein from Clostridium pasteurianum (Cp1) has been determined at 1.08 \u00c5 resolution by multiwavelength anomalous diffraction phasing. Cp1 and the ortholog from Azotobacter vinelandii (Av1) represent two distinct families of nitrogenases, differing primarily by a long insertion in the \u03b1-subunit and a deletion in the \u03b2-subunit of Cp1 relative to Av1. Comparison of these two MoFe protein structures at atomic resolution reveals conserved structural arrangements that are significant to the function of nitrogenase. The FeMo cofactors defining the active sites of the MoFe protein are essentially identical between the two proteins. The surrounding environment is also highly conserved, suggesting that this structural arrangement is crucial for nitrogen reduction. The P clusters are likewise similar, although the surrounding protein and solvent environment is less conserved relative to that of the FeMo cofactor. The P cluster and FeMo cofactor in Av1 and Cp1 are connected through a conserved water tunnel surrounded by similar secondary-structure elements. The long -subunit insertion loop occludes the presumed Fe protein docking surface on Cp1 with few contacts to the remainder of the protein. This makes it plausible that this loop is repositioned to open up the Fe protein docking surface for complex formation.", "date": "2015-02", "date_type": "published", "publication": "Acta Crystallographica Section D: Biological Crystallography", "volume": "71", "number": "2", "publisher": "International Union of Crystallography", "pagerange": "274-282", "id_number": "CaltechAUTHORS:20150310-101137660", "issn": "0907-4449", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150310-101137660", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Sanofi-Aventis Bioengineering Research Program" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" } ] }, "doi": "10.1107/S1399004714025243", "pmcid": "PMC4321486", "primary_object": { "basename": "lp5003.pdf", "url": "https://authors.library.caltech.edu/records/k34wx-08z71/files/lp5003.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Zhang, Li-Mei; Morrison, Christine N.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/d2w3a-x4m12", "eprint_id": 55608, "eprint_status": "archive", "datestamp": "2023-08-20 04:35:29", "lastmod": "2023-10-20 22:25:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tezcan-F-A", "name": { "family": "Tezcan", "given": "F. Akif" }, "orcid": "0000-0002-4733-6500" }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural Evidence for Asymmetrical Nucleotide Interactions in Nitrogenase", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: November 25, 2014, Published: December 18, 2014.\n\nThis work was supported by NIH (GM099813 to F.A.T. and GM045162 to D.C.R.). F.A.T. acknowledges the Frasch Foundation for further support and the Moore Distinguished Scholar program at Caltech. We thank Mika Walton and Debarshi Mustafi for their contributions in the onset of this project, and the Gordon and Betty Moore Foundation for their support of the Molecular Observatory at Caltech. Operations at the Advanced Light Source are funded by the Office of Basic Energy Sciences of the DOE and NIH. Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, IDs 4WZA and 4WZB.\n\nPublished - ja511945e.pdf
Supplemental Material - ja511945e_si_001.pdf
", "abstract": "The roles of ATP hydrolysis in electron-transfer (ET) reactions of the nitrogenase catalytic cycle remain obscure. Here, we present a new structure of a nitrogenase complex crystallized with MgADP and MgAMPPCP, an ATP analogue. In this structure the two nucleotides are bound asymmetrically by the Fe-protein subunits connected to the two different MoFe-protein subunits. This binding mode suggests that ATP hydrolysis and phosphate release may proceed by a stepwise mechanism. Through the associated Fe-protein conformational changes, a stepwise mechanism is anticipated to prolong the lifetime of the Fe-protein-MoFe-protein complex and, in turn, could orchestrate the sequence of intracomplex ET required for substrate reduction.", "date": "2015-01-14", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "137", "number": "1", "publisher": "American Chemical Society", "pagerange": "146-149", "id_number": "CaltechAUTHORS:20150306-133700114", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150306-133700114", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM099813" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Frasch Foundation" }, { "agency": "Caltech Moore Distinguished Scholar Program" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1021/ja511945e", "pmcid": "PMC4304452", "primary_object": { "basename": "ja511945e.pdf", "url": "https://authors.library.caltech.edu/records/d2w3a-x4m12/files/ja511945e.pdf" }, "related_objects": [ { "basename": "ja511945e_si_001.pdf", "url": "https://authors.library.caltech.edu/records/d2w3a-x4m12/files/ja511945e_si_001.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Tezcan, F. Akif; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/v9ha6-bhd92", "eprint_id": 46321, "eprint_status": "archive", "datestamp": "2023-08-20 03:25:08", "lastmod": "2023-10-26 19:40:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wang-Kaituo", "name": { "family": "Wang", "given": "Kaituo" } }, { "id": "Sitsel-O", "name": { "family": "Sitsel", "given": "Oleg" } }, { "id": "Meloni-G", "name": { "family": "Meloni", "given": "Gabriele" } }, { "id": "Autzen-H-E", "name": { "family": "Autzen", "given": "Henriette Elisabeth" } }, { "id": "Andersson-M", "name": { "family": "Andersson", "given": "Magnus" } }, { "id": "Klymchuk-T", "name": { "family": "Klymchuk", "given": "Tetyana" } }, { "id": "Nielsen-A-M", "name": { "family": "Nielsen", "given": "Anna Marie" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Nissen-P-E", "name": { "family": "Nissen", "given": "Poul" } }, { "id": "Gourdon-P", "name": { "family": "Gourdon", "given": "Pontus" } } ] }, "title": "Structure and mechanism of Zn^(2+)- transporting P-type ATPases", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 Macmillan Publishers Limited. \n\nReceived 22 January 2014. Accepted 25 June 2014. Published online 17 August 2014. \n\nWe thank J. L. Karlsen for support with crystallographic computing. O.S. and H.E.A. are supported by the Graduate School of Science and Technology at Aarhus University. G.M. is supported by a Marie Curie International Outgoing Fellowship (European Commission, grant no. 252961). M.A. was supported by a Marie Curie Career Integration Grant (FP7-MC-CIG-618558). P.N. was supported by an advanced research grant from the European Research Council (250322 Biomemos), and P.G. was supported, in the later stage, by the Lundbeck Foundation and the Swedish Research Council (K2013-99X-22251-01-5). We are grateful for assistance with crystal screening from Maxlab, beam lines 911-2/3, and with data collection from the Swiss Light Source, beam line X06SA. Access to synchrotron sources was supported by the Danscatt program of the Danish Council of Independent Research and by BioStruct-X contract 860.\n\nAccepted Version - nihms645060.pdf
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Supplemental Material - nature13618-sf5.jpg
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Supplemental Material - nature13618-sf8.jpg
", "abstract": "Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements. Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2\u00b7P_i) of ZntA from Shigella sonnei, determined at 3.2 \u00c5 and 2.7 \u00c5 resolution, respectively. The structures reveal a similar fold to Cu^+-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn^(2+) ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714. The pathway closes in the E2\u00b7P_i state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn^(2+) release as a built-in counter ion, as has been proposed for H^+-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between P_(IB)-type Zn^(2+)-ATPases and P_(III)-type H^+-ATPases and at the same time show structural features of the extracellular release pathway that resemble P_(II)-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca^(2+)-ATPase (SERCA) and Na^+, K^+-ATPase. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.", "date": "2014-10-23", "date_type": "published", "publication": "Nature", "volume": "514", "number": "7523", "publisher": "Nature Publishing Group", "pagerange": "518-522", "id_number": "CaltechAUTHORS:20140618-084134326", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140618-084134326", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Aarhus University Graduate School of Science and Technology" }, { "agency": "European Commission Marie Curie International Outgoing Fellowship", "grant_number": "252961" }, { "agency": "European Commission Marie Curie Career Integration Grant", "grant_number": "FP7-MC-CIG-618558" }, { "agency": "European Research Council (ERC)", "grant_number": "250322 Biomemos" }, { "agency": "Lundbeck Foundation (Denmark)" }, { "agency": "Swedish Research Council", "grant_number": "K2013-99X-22251-01-5" }, { "agency": "Danish Council of Independent Research" }, { "agency": "BioStruct-X", "grant_number": "860" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1038/nature13618", "pmcid": "PMC4259247", "primary_object": { "basename": "nature13618-sf3.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf3.jpg" }, "related_objects": [ { "basename": "nature13618-sf4.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf4.jpg" }, { "basename": "nature13618-sf5.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf5.jpg" }, { "basename": "nature13618-sf7.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf7.jpg" }, { "basename": "nature13618-sf1.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf1.jpg" }, { "basename": "nature13618-sf2.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf2.jpg" }, { "basename": "nature13618-sf6.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf6.jpg" }, { "basename": "nature13618-sf8.jpg", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nature13618-sf8.jpg" }, { "basename": "nihms645060.pdf", "url": "https://authors.library.caltech.edu/records/v9ha6-bhd92/files/nihms645060.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Wang, Kaituo; Sitsel, Oleg; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wv3ag-mm875", "eprint_id": 50090, "eprint_status": "archive", "datestamp": "2023-08-20 03:17:20", "lastmod": "2023-10-17 22:30:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kamajaya-A", "name": { "family": "Kamajaya", "given": "Aron" } }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Lee-J", "name": { "family": "Lee", "given": "Jonas" } }, { "id": "Reid-M", "name": { "family": "Reid", "given": "Michelle" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Structure of a Conserved Piezo Channel Domain Reveals a Topologically Distinct \u03b2 Sandwich Fold", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 Elsevier Ltd.\n\nReceived: July 1, 2014;\nRevised: August 6, 2014;\nAccepted: August 8, 2014;\nAvailable online 18 September 2014.\n\nWe thank S.E. Kim and A. Patapoutian for providing the C. elegans PIEZO\nconstruct, S. Hess from the Proteome Exploration Laboratory at the Beckman\nInstitute at the California Institute of Technology for mass spectrometry analysis\nof the protein crystals, and P. Nikolovski from the Molecular Observatory\nat the Beckman Institute at the California Institute of Technology. This research\nwas supported by NIH grant GM84211. We acknowledge the Gordon and\nBetty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering\nResearch Program and the Beckman Institute at Caltech for\ngenerous support of the Molecular Observatory at Caltech. Operations at\nSSRL are supported by the U.S. DOE and NIH.\n\nAccepted Version - nihms629482.pdf
", "abstract": "Piezo has recently been identified as a family of\neukaryotic mechanosensitive channels composed\nof subunits containing over 2,000 amino acids,\nwithout recognizable sequence similarity to other\nchannels. Here, we present the crystal structure of\na large, conserved extramembrane domain located\njust before the last predicted transmembrane helix\nof C. elegans PIEZO, which adopts a topologically\ndistinct \u03b2 sandwich fold. The structure was also\ndetermined of a point mutation located on a conserved\nsurface at the position equivalent to the\nhuman PIEZO1 mutation found in dehydrated hereditary\nstomatocytosis patients (M2225R). While the\npoint mutation does not change the overall domain\nstructure, it does alter the surface electrostatic potential\nthat may perturb interactions with a yet-tobe-\nidentified ligand or protein. The lack of structural\nsimilarity between this domain and any previously\ncharacterized fold, including those of eukaryotic\nand bacterial channels, highlights the distinctive\nnature of the Piezo family of eukaryotic mechanosensitive\nchannels.", "date": "2014-10-07", "date_type": "published", "publication": "Structure", "volume": "22", "number": "10", "publisher": "Cell Press", "pagerange": "1520-1527", "id_number": "CaltechAUTHORS:20140929-100953582", "issn": "0969-2126", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140929-100953582", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM84211" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Sanofi-Aventis Bioengineering Research Program" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1016/j.str.2014.08.009", "pmcid": "PMC4192063", "primary_object": { "basename": "nihms629482.pdf", "url": "https://authors.library.caltech.edu/records/wv3ag-mm875/files/nihms629482.pdf" }, "resource_type": "article", "pub_year": "2014", "author_list": "Kamajaya, Aron; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/v5s0d-w6n51", "eprint_id": 47381, "eprint_status": "archive", "datestamp": "2023-08-20 03:02:26", "lastmod": "2023-10-26 20:32:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Spatzal-Thomas", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Perez-Kathryn-A", "name": { "family": "Perez", "given": "Kathryn A." }, "orcid": "0000-0003-1707-5060" }, { "id": "Einsle-Oliver", "name": { "family": "Einsle", "given": "Oliver" }, "orcid": "0000-0001-8722-2893" }, { "id": "Howard-James-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Ligand binding to the FeMo-cofactor: Structures of CO-bound and reactivated nitrogenase", "ispublished": "pub", "full_text_status": "public", "note": "Received for publication 29 May 2014. Accepted for publication 31 July 2014.\n\nWe thank J. Peters, L. Zhang, J. Rittle, C. Morrison, B. Wenke, and\nK. D\u00f6rner for informative discussions. This work was supported by\nNIH grant GM45162 (D.C.R.), Deutsche Forschungsgemeinschaft\ngrants EI-520/7 and RTG 1976, and the European Research Council\nN-ABLE project (O.E.). We gratefully acknowledge the Gordon\nand Betty Moore Foundation, the Beckman Institute, and the\nSanofi-Aventis Bioengineering Research Program at Caltech for\ntheir generous support of the Molecular Observatory at Caltech\nand the staff at Beamline 12\u20132, Stanford Synchrotron Radiation\nLightsource (SSRL), for their assistance with data collection.\nSSRL is operated for the U.S. Department of Energy and supported\nby its Office of Biological and Environmental Research and by\nthe NIH: National Institute of General Medical Sciences (P41GM103393)\nand the National Center for Research Resources (P41RR001209).\nWe thank the Center for Environmental Microbial Interactions for its\nsupport of microbiology research at Caltech. Coordinates and\nstructure factors have been deposited in the Protein Data Bank of\nthe Research Collaboratory for Structural Bioinformatics, with IDs\n4TKV (Av1-CO) and 4TKU (Av1 reactivated).\n\nAccepted Version - nihms619285.pdf
", "abstract": "The mechanism of nitrogenase remains enigmatic, with a major unresolved issue concerning how inhibitors and substrates bind to the active site. We report a crystal structure of carbon monoxide (CO)\u2013inhibited nitrogenase molybdenum-iron (MoFe)\u2013protein at 1.50 angstrom resolution, which reveals a CO molecule bridging Fe2 and Fe6 of the FeMo-cofactor. The \u03bc2 binding geometry is achieved by replacing a belt-sulfur atom (S2B) and highlights the generation of a reactive iron species uncovered by the displacement of sulfur. The CO inhibition is fully reversible as established by regain of enzyme activity and reappearance of S2B in the 1.43 angstrom resolution structure of the reactivated enzyme. The substantial and reversible reorganization of the FeMo-cofactor accompanying CO binding was unanticipated and provides insights into a catalytically competent state of nitrogenase.", "date": "2014-09-26", "date_type": "published", "publication": "Science", "volume": "345", "number": "6204", "publisher": "American Association for the Advancement of Science", "pagerange": "1620-1623", "id_number": "CaltechAUTHORS:20140721-203544454", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140721-203544454", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "Ei-520/7" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "RTG 1976" }, { "agency": "European Research Council (ERC)" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" } ] }, "doi": "10.1126/science.1256679", "pmcid": "PMC4205161", "primary_object": { "basename": "nihms619285.pdf", "url": "https://authors.library.caltech.edu/records/v5s0d-w6n51/files/nihms619285.pdf" }, "resource_type": "article", "pub_year": "2014", "author_list": "Spatzal, Thomas; Perez, Kathryn A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/caepn-gd366", "eprint_id": 48609, "eprint_status": "archive", "datestamp": "2023-08-20 02:15:27", "lastmod": "2023-10-17 19:29:03", "type": "conference_item", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-J-Y", "name": { "family": "Lee", "given": "Jonas Y." } }, { "id": "Yang-J-G", "name": { "family": "Yang", "given": "Janet G." } }, { "id": "Zhitnitsky-D", "name": { "family": "Zhitnitsky", "given": "Daniel" } }, { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural characterization of heavy metal detoxification by a bacterial Atm1-family ABC transporter", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2014 American Chemical Society.", "abstract": "The superfamily of ATP Binding Cassette (ABC) transporters includes importers and exporters that translocate a wide variety of substrates across the cell membrane. Although significant progress has been achieved in the structural anal. of ABC exporters, much less is known about how ABC exporters selectively recognize varying substrates, and couple its binding to ATP hydrolysis. We have addressed these questions by the crystallog. characterization of the dimeric Atm1/ABCB7/HMT1/ABCB6 ortholog from Novosphingobium aromaticivorans DSM 12444 (NaAtm1) at 2.4 Angstrom resoln. The functional characterization of NaAtm1 proved that NaAtm1 is a glutathione (GSH) transporting heavy metal resistance protein. The substrate bound structures elucidated that the amino and carbonyl groups of y-Glu are crit. for GSH binding, and the presence of the second oxidized GSH binding site hints how tetra GSH metal adduct ligands may bind the transporter. Detailed mapping of the binding interactions highlighted the articulated design of ABC exporters with the key ligand interactions positioned at the boundaries between structurally conserved elements, which links ligand binding to the conformational changes underlying ATPase-coupled substrate translocation.", "date": "2014-08", "date_type": "published", "publisher": "Caltech Library", "id_number": "CaltechAUTHORS:20140815-103220170", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140815-103220170", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "resource_type": "conference_item", "pub_year": "2014", "author_list": "Lee, Jonas Y.; Yang, Janet G.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/9jk32-a2g25", "eprint_id": 48803, "eprint_status": "archive", "datestamp": "2023-08-20 01:50:09", "lastmod": "2023-10-17 20:26:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas" }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural and Mechanistic Diversity of ABC Transporters", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2014 The Protein Society. Article first published online: 10 Jul 2014.", "abstract": "ATP Binding Cassette (ABC) transporters constitute a ubiquitous superfamily of integral membrane\nproteins responsible for the ATP powered membrane translocation of a wide variety of substrates. The\nhighly conserved ABC domains defining the superfamily provide the nucleotide-powered engine that\ndrives transport. In contrast, the transmembrane domains creating the translocation pathway are more\nvariable, with three distinct folds currently recognized. Structural analyses of the high affinity methionine\nMetNI importer and of a bacterial homologue of the mitochondrial Atm1 exporter will be discussed within\nthe mechanistic framework of the alternating access model. The interconversion of outward and inward\nfacing conformations of the translocation pathway is coupled to the switching between open and closed\ninterfaces of the ABC subunits that are associated with distinct nucleotide states. As observed for MetNI,\nadditional domains may be present that can regulate transport activity. Building on this qualitative\nmolecular framework for deciphering the transport cycle, an important goal is to develop quantitative\nmodels that detail the kinetic and molecular mechanisms by which ABC transporters utilize the binding\nand hydrolysis of ATP to power substrate translocation.", "date": "2014-07-10", "date_type": "published", "publication": "Protein Science", "volume": "23", "number": "S1", "publisher": "Wiley", "pagerange": "70", "id_number": "CaltechAUTHORS:20140822-093245246", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140822-093245246", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1002/pro.2504", "resource_type": "article", "pub_year": "2014", "author_list": "Rees, Douglas" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/szwze-wkr33", "eprint_id": 54296, "eprint_status": "archive", "datestamp": "2023-08-20 00:15:41", "lastmod": "2023-10-20 15:47:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-J", "name": { "family": "Lee", "given": "Jonas" } }, { "id": "Yang-J", "name": { "family": "Yang", "given": "Janet" } }, { "id": "Zhitnitsky-D", "name": { "family": "Zhitnitsky", "given": "Daniel" } }, { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas" }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural and functional characterization of a heavy metal detoxifying ABC transporter", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2014 by the Federation of American Societies for Experimental Biology. \n\nGrant Funding Source: National Institutes of Health.", "abstract": "The superfamily of ATP Binding Cassette (ABC) transporters includes importers and exporters that translocate a wide variety of substrates across the cell membrane. Although significant progress has been achieved in the structural analysis of ABC exporters, much less is known about how ABC exporters selectively recognize varying substrates, and couple its binding to ATP hydrolysis. We have addressed these questions by the crystallographic and functional characterization of a dimeric Atm1/ABCB7/HMT1/ABCB6 bacterial ortholog. Glutathione and it's derivatives are demonstrated to serve as substrates. In vivo, this transporter confers resistance to silver and mercury toxicity to E. coli, implicating a physiological role in cellular detoxification processes. The 2.4 Angstrom resolution structure allowed detailed mapping of the binding interactions highlighting the articulated design of ABC exporters. The key ligand interactions are positioned at the boundaries between structurally conserved elements, which links ligand binding to the conformational changes underlying ATPase-coupled substrate translocation.", "date": "2014-04", "date_type": "published", "publication": "FASEB Journal", "volume": "28", "number": "1", "publisher": "Federation of American Societies for Experimental Biology", "pagerange": "Art. No. Suppl. 997.2", "id_number": "CaltechAUTHORS:20150202-105705299", "issn": "0892-6638", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150202-105705299", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" } ] }, "resource_type": "article", "pub_year": "2014", "author_list": "Lee, Jonas; Yang, Janet; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yq1y1-vzz06", "eprint_id": 44668, "eprint_status": "archive", "datestamp": "2023-08-19 23:54:48", "lastmod": "2023-10-26 14:51:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Jonas-Y", "name": { "family": "Lee", "given": "Jonas Y." } }, { "id": "Yang-Janet-G", "name": { "family": "Yang", "given": "Janet G." } }, { "id": "Zhitnitsky-D", "name": { "family": "Zhitnitsky", "given": "Daniel" } }, { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural Basis for Heavy Metal Detoxification by an Atm1-Type ABC Exporter", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 American Association for the Advancement of Science.\nReceived for publication 26 September 2013. Accepted for publication 12 February 2014. Supported by NIH grant GM45162. We gratefully acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech, and the staff at Beamline 12-2, Stanford Synchrotron Radiation Lightsource (SSRL), for their assistance with data collection. SSRL is operated for the U.S. Department of Energy and supported by its Office of Basic Energy Research and by National Institute of General Medical Sciences grant P41GM103393 and National Center for Research Resources grant P41RR001209. We thank G. Meloni, J. Kaiser, J. Hoy, R. Lill, S. Molik, I. Booth, S. Conway, and A. Laganowsky for stimulating discussions and providing reagents. Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, with IDs 4MRN, 4MRP, 4MRR, 4MRS, and 4MRV for NaAtm1 in apo form and in complexes with GSH, selenomethionine, GSSG, and GS-Hg, respectively.\n\nAccepted Version - nihms618661.pdf
Supplemental Material - Lee.SM.pdf
", "abstract": "Although substantial progress has been achieved in the structural analysis of exporters from the superfamily of adenosine triphosphate (ATP)\u2013binding cassette (ABC) transporters, much less is known about how they selectively recognize substrates and how substrate binding is coupled to ATP hydrolysis. We have addressed these questions through crystallographic analysis of the Atm1/ABCB7/HMT1/ABCB6 ortholog from Novosphingobium aromaticivorans DSM 12444, NaAtm1, at 2.4 angstrom resolution. Consistent with a physiological role in cellular detoxification processes, functional studies showed that glutathione derivatives can serve as substrates for NaAtm1 and that its overexpression in Escherichia coli confers protection against silver and mercury toxicity. The glutathione binding site highlights the articulated design of ABC exporters, with ligands and nucleotides spanning structurally conserved elements to create adaptable interfaces accommodating conformational rearrangements during the transport cycle.", "date": "2014-03-07", "date_type": "published", "publication": "Science", "volume": "343", "number": "6175", "publisher": "American Association for the Advancement of Science", "pagerange": "1133-1136", "id_number": "CaltechAUTHORS:20140404-150104796", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140404-150104796", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Caltech Sanofi-Aventis Bioengineering Research Program" }, { "agency": "Department of Energy (DOE)" }, { "agency": "National Institute of General Medical Sciences (NIGMS)", "grant_number": "P41GM103393" }, { "agency": "National Center for Research Resources (NCRR)", "grant_number": "P41RR001209" } ] }, "doi": "10.1126/science.1246489", "pmcid": "PMC4151877", "primary_object": { "basename": "Lee.SM.pdf", "url": "https://authors.library.caltech.edu/records/yq1y1-vzz06/files/Lee.SM.pdf" }, "related_objects": [ { "basename": "nihms618661.pdf", "url": "https://authors.library.caltech.edu/records/yq1y1-vzz06/files/nihms618661.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Lee, Jonas Y.; Yang, Janet G.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/t5dyj-c7h50", "eprint_id": 45206, "eprint_status": "archive", "datestamp": "2023-08-19 23:40:11", "lastmod": "2023-10-26 17:51:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "L." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Shining Light on the Metal Sites in Nitrogenase MoFe-protein by X-ray Anomalous Diffraction", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2014 Springer. CONTROL ID: 1720516", "abstract": "In the process of biological nitrogen fixation, the nitrogenase MoFe-protein catalyzes the reduction dinitrogen to ammonia at the FeMo-cofactor, upon receiving the electrons from the donor via Fe-protein.", "date": "2014-03", "date_type": "published", "publication": "Journal of Biological Inorganic Chemistry", "volume": "19", "number": "S1", "publisher": "Springer", "pagerange": "S84", "id_number": "CaltechAUTHORS:20140425-073027224", "issn": "0949-8257", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140425-073027224", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1007/s00775-014-1095-8", "resource_type": "article", "pub_year": "2014", "author_list": "Zhang, L. and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tq0vg-n0990", "eprint_id": 47129, "eprint_status": "archive", "datestamp": "2023-08-19 23:16:05", "lastmod": "2023-10-26 20:20:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural and Mechanistic Diversity of ABC Transporters", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2014 Biophysical Society. Published by Elsevier Inc.", "abstract": "ATP Binding Cassette (ABC) transporters constitute a ubiquitous superfamily of integral membrane proteins responsible for the ATP powered membrane translocation of a wide variety of substrates. The highly conserved ABC domains defining the superfamily provide the nucleotide-powered engine that drives transport. In contrast, the transmembrane domains creating the translocation pathway are more variable, with three distinct folds currently recognized. Structural analyses of the high affinity methionine MetNI importer and of a bacterial homologue of the mitochondrial Atm1 exporter will be discussed within the mechanistic framework of the alternating access model. The interconversion of outward and inward facing conformations of the translocation pathway is coupled to the switching between open and closed interfaces of the ABC subunits that are associated with distinct nucleotide states. As observed for MetNI, additional domains may be present that can regulate transport activity. Building on this qualitative molecular framework for deciphering the transport cycle, an important goal is to develop quantitative models that detail the kinetic and molecular mechanisms by which ABC transporters utilize the binding and hydrolysis of ATP to power substrate translocation.", "date": "2014-01-28", "date_type": "published", "publication": "Biophysical Journal", "volume": "106", "number": "2", "publisher": "Biophysical Society", "pagerange": "434A", "id_number": "CaltechAUTHORS:20140710-093656033", "issn": "0006-3495", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140710-093656033", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/j.bpj.2013.11.2443", "resource_type": "article", "pub_year": "2014", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sm3pb-a1w75", "eprint_id": 43359, "eprint_status": "archive", "datestamp": "2023-08-19 23:11:28", "lastmod": "2023-10-25 23:29:42", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yang-Kun-Yun", "name": { "family": "Yang", "given": "Kun-Yun" } }, { "id": "Haynes-C-A", "name": { "family": "Haynes", "given": "Chad A." } }, { "id": "Spatzal-T", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } } ] }, "title": "Turnover-Dependent Inactivation of the Nitrogenase MoFe-Protein at High pH", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 American Chemical Society.\nReceived: October 30, 2013;\nRevised: December 12, 2013.\nPublication Date (Web): December 24, 2013.\nThe assistance of Dr. Jens Kaiser and Dr. Nathan Dalleska is\nappreciated. We acknowledge the Gordon and Betty Moore\nFoundation, the Beckman Institute, and the Sanofi\u2212Aventis\nBioengineering Research Program at Caltech for their generous\nsupport of the Molecular Observatory at Caltech. This project\nbenefited from the use of instrumentation made available by the\nCaltech Environmental Analysis Center. Portions of this\nresearch were conducted at the Stanford Synchrotron Radiation\nLightsource (SSRL), a Directorate of SLAC National\nAccelerator Laboratory and an Office of Science User Facility\noperated for the U.S. Department of Energy Office of Science\nby Stanford University. The SSRL Structural Molecular Biology\nProgram is supported by the Department of Energy Office of\nBiological and Environmental Research and by the National\nInstitutes of Health, National Center for Research Resources,\nBiomedical Technology Program (P41RR001209), and the\nNational Institute of General Medical Sciences.\n\nPublished - Yang_2014.pdf
Supplemental Material - bi4014769_si_001.pdf
", "abstract": "Proton uptake accompanies the reduction of all known substrates by nitrogenase. As a consequence, a higher pH should limit the availability of protons as a substrate essential for turnover, thereby increasing the proportion of more highly reduced forms of the enzyme for further study. The utility of the high-pH approach would appear to be problematic in view of the observation reported by Pham and Burgess [(1993) Biochemistry 32, 13725\u201313731] that the MoFe-protein undergoes irreversible protein denaturation above pH 8.65. In contrast, we found by both enzyme activity and crystallographic analyses that the MoFe-protein is stable when incubated at pH 9.5. We did observe, however, that at higher pHs and under turnover conditions, the MoFe-protein is slowly inactivated. While a normal, albeit low, level of substrate reduction occurs under these conditions, the MoFe-protein undergoes a complex transformation; initially, the enzyme is reversibly inhibited for substrate reduction at pH 9.5, yet in a second, slower process, the MoFe-protein becomes irreversibly inactivated as measured by substrate reduction activity at the optimal pH of 7.8. The final inactivated MoFe-protein has an increased hydrodynamic radius compared to that of the native MoFe-protein, yet it has a full complement of iron and molybdenum. Significantly, the modified MoFe-protein retains the ability to specifically interact with its nitrogenase partner, the Fe-protein, as judged by the support of ATP hydrolysis and by formation of a tight complex with the Fe-protein in the presence of ATP and aluminum fluoride. The turnover-dependent inactivation coupled to conformational change suggests a mechanism-based transformation that may provide a new probe of nitrogenase catalysis.", "date": "2014-01-21", "date_type": "published", "publication": "Biochemistry", "volume": "53", "number": "2", "publisher": "American Chemical Society", "pagerange": "333-343", "id_number": "CaltechAUTHORS:20140114-130352029", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140114-130352029", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Caltech Sanofi-Aventis Bioengineering Research Program" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "National Institute of General Medical Sciences" } ] }, "doi": "10.1021/bi4014769", "pmcid": "PMC3932303", "primary_object": { "basename": "Yang_2014.pdf", "url": "https://authors.library.caltech.edu/records/sm3pb-a1w75/files/Yang_2014.pdf" }, "related_objects": [ { "basename": "bi4014769_si_001.pdf", "url": "https://authors.library.caltech.edu/records/sm3pb-a1w75/files/bi4014769_si_001.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Yang, Kun-Yun; Haynes, Chad A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/582q6-0rb63", "eprint_id": 44074, "eprint_status": "archive", "datestamp": "2023-08-19 23:09:49", "lastmod": "2023-10-26 00:09:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Meloni-G", "name": { "family": "Meloni", "given": "Gabriele" } }, { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Transmembrane Type-2-like Cu^(2+) Site in the P_(1B-3)-type ATPase CopB: Implications for Metal Selectivity", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 American Chemical Society. \n\nReceived: August 12, 2013; accepted: October 21, 2013; published: October 21, 2013. \n\nThe work was supported by National Institutes of Health\n(NIH) (grant No. GM45162 to D.C.R.), by a Swiss National\nScience Foundation fellowship for prospective researchers (to G.M.), by a Marie Curie International Outgoing Fellowship (European Commission, grant No. 252961 to G.M.), and by a NSERC PDF award (to L.Z.). We thank Poul Nissen\n(University of Aarhus, Denmark) for supervising the Marie\nCurie Fellowship. We thank the staff at Beamline 7-3, Stanford Synchrotron Radiation Lightsource (SSRL), and staff at HXMA Beamline, Canadian Light Source (CLS). SSRL is operated for the DOE and supported by OBER and by the NIH, NIGMS (P41GM103393), and the NCRR (P41RR001209). CLS is\nsupported by NSERC, NRC, CIHR, and the University of\nSaskatchewan. We thank O. Lewinson and A. T. Lee for\nproviding the full-length cDNA of CopB and A. Di Bilio for\nassistance with EPR measurements. This project benefited from discussion with Nathan Dalleska and instrumentation made available by the Caltech Environmental Analysis Center.\n\nAccepted Version - nihms537544.pdf
Supplemental Material - cb400603t_si_001.pdf
", "abstract": "Metal selectivity in P_(1B)-type ATPase transporters is determined by conserved amino acid residues in their transmembrane helices responsible for metal binding and transport across the cellular membrane. The Cu^(2+)-selective CopB from Archaeoglobus fulgidus has been investigated to explore the coordination chemistry of the transition metal binding sites in P_(1B-3)-type ATPases. Electronic absorption, electron paramagnetic resonance, and X-ray absorption spectroscopic studies indicate the presence of a high-affinity transmembrane Type-2-like Cu^(2+) center in which a single cupric ion is coordinated in a distorted square pyramidal geometry by mixed nitrogen/oxygen and sulfur ligands.", "date": "2014-01-17", "date_type": "published", "publication": "ACS Chemical Biology", "volume": "9", "number": "1", "publisher": "American Chemical Society", "pagerange": "116-121", "id_number": "CaltechAUTHORS:20140228-145854857", "issn": "1554-8929", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140228-145854857", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "Marie Curie Fellowship", "grant_number": "252961" }, { "agency": "OBER" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "National Research Council of Canada" }, { "agency": "Canadian Institutes of Health Research (CIHR)" }, { "agency": "University of Saskatchewan" } ] }, "doi": "10.1021/cb400603t", "pmcid": "PMC3947036", "primary_object": { "basename": "cb400603t_si_001.pdf", "url": "https://authors.library.caltech.edu/records/582q6-0rb63/files/cb400603t_si_001.pdf" }, "related_objects": [ { "basename": "nihms537544.pdf", "url": "https://authors.library.caltech.edu/records/582q6-0rb63/files/nihms537544.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Meloni, Gabriele; Zhang, Limei; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pxwvg-51p49", "eprint_id": 43803, "eprint_status": "archive", "datestamp": "2023-08-22 11:26:57", "lastmod": "2023-10-25 23:53:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Basta-T", "name": { "family": "Basta", "given": "Tamara" } }, { "id": "Wu-Hsin-Jui", "name": { "family": "Wu", "given": "Hsin-Jui" } }, { "id": "Morphew-M-K", "name": { "family": "Morphew", "given": "Mary K." } }, { "id": "Lee-Jonas-Yun", "name": { "family": "Lee", "given": "Jonas" } }, { "id": "Ghosh-N", "name": { "family": "Ghosh", "given": "Nilanjan" } }, { "id": "Lai-Jeffrey", "name": { "family": "Lai", "given": "Jeffrey" } }, { "id": "Heumann-J-M", "name": { "family": "Heumann", "given": "John M." } }, { "id": "Wang-Keeshia", "name": { "family": "Wang", "given": "Keeshia" } }, { "id": "Lee-Y-C", "name": { "family": "Lee", "given": "Y. C." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } } ] }, "title": "Self-assembled lipid and membrane protein polyhedral nanoparticles", "ispublished": "pub", "full_text_status": "public", "keywords": "membrane protein structure; proteoliposomes; electron microscopy; microfluidic devices", "note": "\u00a9 2014 National Academy of Sciences.\n\nContributed by Douglas C. Rees, November 26, 2013 (sent for review January 28, 2012).\n\nWe thank our colleagues at the University of Colorado\nand California Institute of Technology (Caltech) for helpful comments and criticisms, Randal Bass (Caltech) for providing initial MscS samples, Mark Yeager and Brad Bennett (University of Virginia) for providing samples of\nCx26, Steven Ludtke (Baylor University) for EMAN advice, Rob Phillips and Christoph Haselwandter (Caltech) for discussions on polyhedral symmetry, and Chris Arthur (Oregon Health and Science University) and Axel Brilot\n(Brandeis University) for assistance with image scanning. Molecular graphics images were produced using the University of California, San Francisco (UCSF) Chimera package from the Resource for Biocomputing, Visualization,\nand Informatics at UCSF (supported by NIH-P41RR001081). Electron microscopy was performed in the Laboratory for 3D Electron Microscopy of Cells at the University of Colorado (supported by NIH-P41GM103431-42). This work was supported in part by a National Institutes of Health (NIH) Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) Award (to M.H.B.S.), a Howard Hughes Medical Institute Collaborative Innovation Award (to D.C.R. and M.H.B.S.), and NIH Grant GM084211 (to D.C.R.).\n\nAuthor contributions: T.B., H.-J.W., M.K.M., Y.C.L., D.C.R., and M.H.B.S. designed research;\nT.B., H.-J.W., M.K.M., J. Lee, N.G., J. Lai, K.W., D.C.R., and M.H.B.S. performed research;\nJ. Lee, J. Lai, J.M.H., K.W., and Y.C.L. contributed new reagents/analytic tools; T.B., H.-J.W.,\nM.K.M., J. Lee, N.G., J.M.H., Y.C.L., D.C.R., and M.H.B.S. analyzed data; and D.C.R.\nand M.H.B.S. wrote the paper.\n\nPublished - PNAS-2014-Basta-670-4.pdf
Supplemental Material - pnas.201321936SI.pdf
", "abstract": "We demonstrate that membrane proteins and phospholipids can\nself-assemble into polyhedral arrangements suitable for structural\nanalysis. Using the Escherichia coli mechanosensitive channel of\nsmall conductance (MscS) as a model protein, we prepared membrane\nprotein polyhedral nanoparticles (MPPNs) with uniform radii\nof \u223c20 nm. Electron cryotomographic analysis established that\nthese MPPNs contain 24 MscS heptamers related by octahedral\nsymmetry. Subsequent single-particle electron cryomicroscopy yielded\na reconstruction at \u223c1-nm resolution, revealing a conformation\nclosely resembling the nonconducting state. The generality of this\napproach has been addressed by the successful preparation ofMPPNs\nfor two unrelated proteins, the mechanosensitive channel of large\nconductance and the connexon Cx26, using a recently devised microfluidics-\nbased free interface diffusion system. MPPNs provide not\nonly a starting point for the structural analysis of membrane proteins\nin a phospholipid environment, but their closed surfaces\nshould facilitate studies in the presence of physiological transmembrane\ngradients, in addition to potential applications as drug delivery\ncarriers or as templates for inorganic nanoparticle formation.", "date": "2014-01-14", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "111", "number": "2", "publisher": "National Academy of Sciences", "pagerange": "670-674", "id_number": "CaltechAUTHORS:20140213-094220727", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140213-094220727", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P41RR001081" }, { "agency": "NIH", "grant_number": "P41GM103431-42" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM084211" } ] }, "doi": "10.1073/pnas.1321936111", "pmcid": "PMC3896197", "primary_object": { "basename": "PNAS-2014-Basta-670-4.pdf", "url": "https://authors.library.caltech.edu/records/pxwvg-51p49/files/PNAS-2014-Basta-670-4.pdf" }, "related_objects": [ { "basename": "pnas.201321936SI.pdf", "url": "https://authors.library.caltech.edu/records/pxwvg-51p49/files/pnas.201321936SI.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Basta, Tamara; Wu, Hsin-Jui; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tgpf0-whq78", "eprint_id": 42246, "eprint_status": "archive", "datestamp": "2023-08-22 10:42:35", "lastmod": "2023-10-25 15:46:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Walton-Troy-A", "name": { "family": "Walton", "given": "Troy A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure and stability of the C-terminal helical bundle of the E. coli mechanosensitive channel of large conductance", "ispublished": "pub", "full_text_status": "restricted", "keywords": "protein structure; mechanosensitive channels; membrane proteins; coiled coils", "note": "\u00a9 2013 The Protein Society. Published by Wiley-Blackwell. \n\nReceived 9 July 2013; Revised 12 August 2013; Accepted 14 August 2013. \n\nGrant sponsor: NIH; Grant number: 084211. \n\nThe authors thank Jens Kaiser, Eric Johnson, and Matt Sazinsky for assistance with crystallography and members of the Rees laboratory for helpful comments. CD data were collected in the Beckman Institute Laser Resource Center. They also thank the Gordon and Betty Moore Foundation and the Beckman Institute for their generous support of the Molecular Observatory at Caltech. Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL), a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the US Department of Energy Office of Science by Stanford University. \n\nThe SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program (P41RR001209), and the National Institute of General Medical Sciences. Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, with ID 4LKU.", "abstract": "The crystal structure of the cytoplasmic domain (CTD) from the mechanosensitive channel of large conductance (MscL) in E. coli has been determined at 1.45 \u00c5 resolution. This domain forms a pentameric coiled coil similar to that observed in the structure of MscL from M. tuberculosis and also found in the cartilage oligomeric matrix protein (COMPcc). It contains canonical hydrophobic and atypical ionic interactions compared to previously characterized coiled coil structures. Thermodynamic analysis indicates that while the free EcMscL-CTD is less stable than other coiled coils, it is likely to remain folded in context of the full-length channel.", "date": "2013-11", "date_type": "published", "publication": "Protein Science", "volume": "22", "number": "11", "publisher": "Wiley", "pagerange": "1592-1601", "id_number": "CaltechAUTHORS:20131105-094857416", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131105-094857416", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "084211" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "National Institute of General Medical Sciences" } ] }, "doi": "10.1002/pro.2360", "pmcid": "PMC3831674", "resource_type": "article", "pub_year": "2013", "author_list": "Walton, Troy A. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wt3gb-f3613", "eprint_id": 45473, "eprint_status": "archive", "datestamp": "2023-08-19 21:42:46", "lastmod": "2023-10-26 18:00:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wu-H-J", "name": { "family": "Wu", "given": "H.-J." } }, { "id": "Basta-T", "name": { "family": "Basta", "given": "T." } }, { "id": "Morphew-M", "name": { "family": "Morphew", "given": "M." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "M. H. B." } }, { "id": "Lee-Y-C", "name": { "family": "Lee", "given": "Y. C." } } ] }, "title": "Microfluidic device for super-fast evaluation of membrane protein nanoparticle formation", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2013 The Institution of Engineering and Technology.\n\nPublished in Micro & Nano Letters; Received on 25th April 2013; Revised on 8th July 2013; Accepted on 17th July 2013.\n\nThis work was supported by the Howard\nHughes Medical Institute (HHMI). The authors thank their\ncolleagues in the Departments of Mechanical Engineering, and\nMolecular, Cellular and Developmental Biology (MCDB) of the\nUniversity of Colorado at Boulder, and the California Institute of\nTechnology at Pasadena for helpful support and comments.", "abstract": "Membrane proteins embedded in bilayer lipids of cell membrane have unique functions including inter-cell communication and ionic/molecular transport. To understand the structure and function of the membrane protein embedded in a native biological bilayer lipid\nenvironment is a major research area in biology. A reconstitution/crystallisation process of membrane proteins and lipids can form virus-like\nnanoparticles, and have important potential applications in drug design and drug delivery. Earlier studies used a standard dialysis\nprocess that is inherently low-throughput, time consuming (days to weeks) and costly in protein materials. In this reported work a new\nmicrofluidic device is demonstrated to rapidly form membrane protein lipid nanoparticles in an extremely short period (seconds). The\nreconstitution process occurs using a continuous flow dominated by convection-diffusion phenomena in the microfluidic channel, which\ncan form protein/lipid nanoparticles using only nanolitres or picolitres of protein sample. Moreover, a controllable syringe pump is used to\ntest a combination of conditions, rather than using inefficient hand pipetting. Therefore this novel microfluidic device has an ability to\nrapidly form uniform membrane protein/lipid nanoparticles, and the authors believe that this new method will make a transformative\nimpact on commercial applications in a variety of areas from biology to pharmacology.", "date": "2013-10", "date_type": "published", "publication": "Micro and Nano Letters", "volume": "8", "number": "10", "publisher": "Institution of Engineering and Technology", "pagerange": "672-675", "id_number": "CaltechAUTHORS:20140505-081924948", "issn": "1750-0443", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140505-081924948", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1049/mnl.2013.0216", "resource_type": "article", "pub_year": "2013", "author_list": "Wu, H.-J.; Basta, T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/s0wwf-3kh06", "eprint_id": 42229, "eprint_status": "archive", "datestamp": "2023-08-22 10:25:07", "lastmod": "2023-10-25 15:45:54", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Meloni-G", "name": { "family": "Meloni", "given": "Gabriele" } }, { "id": "Yang-Kun-Yun", "name": { "family": "Yang", "given": "Kun-Yun" } }, { "id": "Spatzal-T", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Sixteenth Iron in the Nitrogenase MoFe Protein", "ispublished": "pub", "full_text_status": "public", "keywords": "iron; metalloproteins; multiple-wavelength anomalous diffraction; nitrogen fixation; nitrogenases", "note": "\u00a9 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: May 6, 2013. Published online: August 21, 2013. \n\nThe work was supported by the NIH (grant GM45162 to D.C.R.), NSERC PDF award (to L.M.Z.), and Deutsche Forschungsgemeinschaft (grants Ei-520/7 to O.E., An-676/1 to S.L.A.A., and IRTG 1478). G.M. is a Marie Curie International Outgoing Fellow (European Commission, grant no. 252961). We thank staff at Beamline 12\u20132, Stanford Synchrotron Radiation Lightsource (SSRL) and staff at HXMA Beamline, Canada Light Source (CLS). SSRL is operated for the DOE and supported by its OBER and by the NIH, NIGMS (P41GM103393) and the NCRR (P41RR001209). CLS is supported by NSERC, NRC, CIHR, and the University of Saskatchewan. We acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech. The assistance of Nathan Dalleska and the resources of the Caltech Environmental Analysis Center are greatly appreciated.\n\nAccepted Version - nihms-534176.pdf
", "abstract": "Another iron in the fire: X-ray anomalous diffraction studies on the nitrogenase MoFe protein show the presence of a mononuclear iron site, designated as Fe16, which was previously identified as either Ca^(2+) or Mg^(2+). The position of the absorption edge indicates that this site is in the oxidation state +2. The high sequence conservation of the residues coordinated to Fe16 emphasizes the potential importance of the site in nitrogenase.", "date": "2013-09-27", "date_type": "published", "publication": "Angewandte Chemie International Edition", "volume": "52", "number": "40", "publisher": "Wiley", "pagerange": "10529-10532", "id_number": "CaltechAUTHORS:20131104-141900919", "issn": "1433-7851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131104-141900919", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "Ei-520/7" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "An-676/1" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "IRTG 1478" }, { "agency": "Marie Curie Fellowship", "grant_number": "252961" }, { "agency": "OBER" }, { "agency": "NIH", "grant_number": "P41GM103393" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "National Research Council of Canada" }, { "agency": "Canadian Institutes of Health Research (CIHR)" }, { "agency": "University of Saskatchewan" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Caltech Sanofi-Aventis Bioengineering Research Program" } ] }, "doi": "10.1002/anie.201303877", "pmcid": "PMC3891402", "primary_object": { "basename": "nihms-534176.pdf", "url": "https://authors.library.caltech.edu/records/s0wwf-3kh06/files/nihms-534176.pdf" }, "resource_type": "article", "pub_year": "2013", "author_list": "Zhang, Limei; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/msvyw-7dz46", "eprint_id": 42502, "eprint_status": "archive", "datestamp": "2023-08-19 21:23:50", "lastmod": "2023-10-25 16:43:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Kechris-K-J", "name": { "family": "Kechris", "given": "Katerina J." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Glazer-A-N", "name": { "family": "Glazer", "given": "Aleander N." } } ] }, "title": "Multiple Amino Acid Sequence Alignment Nitrogenase Component 1: Insights into Phylogenetics and Structure-Function Relationships", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 Howard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\n\nReceived June 17, 2013; Accepted July 18, 2013; Published September 3, 2013.\n\nThis work was supported by National Institutes of Health Grant GM45162 to DCR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\n\nAuthor Contributions:\nConceived and designed the experiments: JBH KJK DCR ANG. Analyzed\nthe data: JBH KJK DCR ANG. Wrote the paper: JBH KJK DCR ANG.\n\nPublished - journal.pone.0072751.pdf
Supplemental Material - journal.pone.0072751.s001.pdf
Supplemental Material - journal.pone.0072751.s002.pdf
Supplemental Material - journal.pone.0072751.s003.pdf
Supplemental Material - journal.pone.0072751.s004.pdf
Supplemental Material - journal.pone.0072751.s005.pdf
Supplemental Material - journal.pone.0072751.s006.pdf
Supplemental Material - journal.pone.0072751.s007.pdf
Supplemental Material - journal.pone.0072751.s008.pdf
Supplemental Material - journal.pone.0072751.s009.pdf
Supplemental Material - journal.pone.0072751.s010.pdf
Supplemental Material - journal.pone.0072751.s011.pdf
", "abstract": "Amino acid residues critical for a protein's structure-function are retained by natural selection and these residues are identified by the level of variance in co-aligned homologous protein sequences. The relevant residues in the nitrogen fixation Component 1 \u03b1- and \u03b2-subunits were identified by the alignment of 95 protein sequences. Proteins were included from species encompassing multiple microbial phyla and diverse ecological niches as well as the nitrogen fixation genotypes, anf, nif, and vnf, which encode proteins associated with cofactors differing at one metal site. After adjusting for differences in sequence length, insertions, and deletions, the remaining >85% of the sequence co-aligned the subunits from the three genotypes. Six Groups, designated Anf, Vnf , and Nif I-IV, were assigned based upon genetic origin, sequence adjustments, and conserved residues. Both subunits subdivided into the same groups. Invariant and single variant residues were identified and were defined as \"core\" for nitrogenase function. Three species in Group Nif-III, Candidatus Desulforudis audaxviator, Desulfotomaculum kuznetsovii, and Thermodesulfatator indicus, were found to have a seleno-cysteine that replaces one cysteinyl ligand of the 8Fe:7S, P-cluster. Subsets of invariant residues, limited to individual groups, were identified; these unique residues help identify the gene of origin (anf, nif, or vnf) yet should not be considered diagnostic of the metal content of associated cofactors. Fourteen of the 19 residues that compose the cofactor pocket are invariant or single variant; the other five residues are highly variable but do not correlate with the putative metal content of the cofactor. The variable residues are clustered on one side of the cofactor, away from other functional centers in the three dimensional structure. Many of the invariant and single variant residues were not previously recognized as potentially critical and their identification provides the bases for new analyses of the three-dimensional structure and for mutagenesis studies.", "date": "2013-09-03", "date_type": "published", "publication": "PLoS ONE", "volume": "8", "number": "9", "publisher": "Public Library of Science", "pagerange": "Art. No. e72751", "id_number": "CaltechAUTHORS:20131115-120001802", "issn": "1932-6203", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131115-120001802", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1371/journal.pone.0072751", "pmcid": "PMC3760896", "primary_object": { "basename": "journal.pone.0072751.s009.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s009.pdf" }, "related_objects": [ { "basename": "journal.pone.0072751.s002.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s002.pdf" }, { "basename": "journal.pone.0072751.s003.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s003.pdf" }, { "basename": "journal.pone.0072751.s005.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s005.pdf" }, { "basename": "journal.pone.0072751.s006.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s006.pdf" }, { "basename": "journal.pone.0072751.s007.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s007.pdf" }, { "basename": "journal.pone.0072751.s008.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s008.pdf" }, { "basename": "journal.pone.0072751.s010.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s010.pdf" }, { "basename": "journal.pone.0072751.s011.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s011.pdf" }, { "basename": "journal.pone.0072751.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.pdf" }, { "basename": "journal.pone.0072751.s001.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s001.pdf" }, { "basename": "journal.pone.0072751.s004.pdf", "url": "https://authors.library.caltech.edu/records/msvyw-7dz46/files/journal.pone.0072751.s004.pdf" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Howard, James B.; Kechris, Katerina J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/s3eq7-k6m64", "eprint_id": 73732, "eprint_status": "archive", "datestamp": "2023-08-19 19:27:28", "lastmod": "2023-10-24 16:24:02", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wu-Hsin-Jui", "name": { "family": "Wu", "given": "Hsin-Jui" } }, { "id": "Basta-T", "name": { "family": "Basta", "given": "Tamara" } }, { "id": "Morphew-M", "name": { "family": "Morphew", "given": "Mary" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Lee-Y-C", "name": { "family": "Lee", "given": "Y. C." } } ] }, "title": "Microfluidic device for super-fast evaluation of membrane protein crystallization", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2013 IEEE. \n\nThis work was supported by Howard Hughes Medical Institute \n(HHMI). We thank our colleagues in Departments of Mechanical Engineering, and Molecular, Cellular and Developmental Biology (MCDB) of University of Colorado at Boulder, and California Institute of Technology at Pasadena for helpful supports and comments.", "abstract": "Membrane proteins embedded in bi-layer lipids of cell membrane have unique functions including inter-cell communication, ions/molecules transport. And there is more than 50% of drug design emphasizes on membrane proteins specifically studying on their structure and formation. Recently we reported the structural and functional studies of membrane protein lipid nanoparticles in native biological membrane. This virus-like nanoparticle formed by a self-assembly crystallization process of membrane protein and lipids is critical to pharmaceutical industrial. These nanoparticles have a variety of potential applications in drug delivery and drug design that can carry specific the membrane protein on aim or release control. The previous studies stay on an inefficient method with a standard dialysis process that has low-throughput, time consumption, and protein sample waste. However, the interdisciplinary cooperation between in biology and Micro electro mechanical systems (MEMS) has been tremendous developed such as Bio-MEMS and Lab-on-achip technologies. Here we demonstrate a new concept with a high-throughput membraneless microfluidic device to fast produce the reconstitution of membrane protein nanoparticles. The reconstitution process in continuous micro flow dominated by convection-diffusion phenomena in microfluidic channel can be completed in seconds to form protein/lipid particles under multiple conditions applied. The controllable syringe pumps is used to test a combination of conditions rather than using inefficient hand pipette. Moreover this novel microfluidic device can save protein sample consumption down to only nanoliter or picoliter. By using this device, we have an ability to rapidly form uniform membrane protein lipid nanoparticles and we believe this new method will make a transformative impact to commercial applications in variety of areas from biology to pharmacology.", "date": "2013-04", "date_type": "published", "publisher": "IEEE", "place_of_pub": "Piscataway, NJ", "pagerange": "84-87", "id_number": "CaltechAUTHORS:20170125-144353492", "isbn": "978-1-4673-6352-5", "book_title": "8th Annual IEEE International Conference on Nano/Micro Engineered and Molecular Systems", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170125-144353492", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1109/NEMS.2013.6559687", "resource_type": "book_section", "pub_year": "2013", "author_list": "Wu, Hsin-Jui; Basta, Tamara; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0skbc-ey411", "eprint_id": 38154, "eprint_status": "archive", "datestamp": "2023-08-22 08:59:20", "lastmod": "2023-10-23 19:52:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lai-Jeffrey-Y", "name": { "family": "Lai", "given": "Jeffrey Y." } }, { "id": "Poon-Yan-Shuen", "name": { "family": "Poon", "given": "Yan Shuen" } }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Open and shut: Crystal structures of the dodecylmaltoside solubilized mechanosensitive channel of small conductance from Escherichia coli and Helicobacter pylori at 4.4 \u00c5 and 4.1 \u00c5 resolutions", "ispublished": "pub", "full_text_status": "public", "keywords": "mechanosensitive channel; MscS; membrane protein structure; protein structure", "note": "\u00a9 2013 The Protein Society. \nPublished by Wiley-Blackwell.\nReceived 9 November 2012; Revised 15 January 2013; Accepted 15 January 2013. Published online 21 Feb 2013. \n\nJeffrey Y. Lai and Yan Shuen Poon contributed equally to this work. Grant sponsor: NIH; Grant number: GM084211. \n\nWe thank the Gordon and Betty Moore Foundation for\ntheir generous support of the Molecular Observatory at Caltech. Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL), a Directorate of SLAC National Accelerator Laboratory, and an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program (P41RR001209), and the National Institute of General Medical Sciences. Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, with IDs 4HWA and 4HW9 for the EcMscS and\nHpMscS structures, respectively.\n\nSupplemental Material - PRO_2222_sm_SuppInfo.pdf
", "abstract": "The mechanosensitive channel of small conductance (MscS) contributes to the survival of bacteria during osmotic downshock by transiently opening large diameter pores for the efflux of cellular contents before the membrane ruptures. Two crystal structures of the Escherichia coli MscS are currently available, the wild type protein in a nonconducting state at 3.7 \u00c5 resolution (Bass et al., Science 2002; 298:1582\u20131587) and the Ala106Val variant in an open state at 3.45 \u00c5 resolution (Wang et al., Science 2008; 321:1179\u20131183). Both structures used protein solubilized in the detergent fos-choline-14. We report here crystal structures of MscS from E. coli and Helicobacter pylori solubilized in the detergent \u03b2-dodecylmaltoside at resolutions of 4.4 and 4.2 \u00c5, respectively. While the cytoplasmic domains are unchanged in these structures, distinct conformations of the transmembrane domains are observed. Intriguingly, \u03b2-dodecylmaltoside solubilized wild type E. coli MscS adopts the open state structure of A106V E. coli MscS, while H. pylori MscS resembles the nonconducting state structure observed for fos-choline-14 solubilized E. coli MscS. These results highlight the sensitivity of membrane protein conformational equilibria to variations in detergent, crystallization conditions, and protein sequence.", "date": "2013-04", "date_type": "published", "publication": "Protein Science", "volume": "22", "number": "4", "publisher": "Wiley", "pagerange": "502-509", "id_number": "CaltechAUTHORS:20130429-105328041", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130429-105328041", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM084211" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "P41RR001209" }, { "agency": "National Institute of General Medical Sciences" } ] }, "doi": "10.1002/pro.2222", "pmcid": "PMC3610056", "primary_object": { "basename": "PRO_2222_sm_SuppInfo.pdf", "url": "https://authors.library.caltech.edu/records/0skbc-ey411/files/PRO_2222_sm_SuppInfo.pdf" }, "resource_type": "article", "pub_year": "2013", "author_list": "Lai, Jeffrey Y.; Poon, Yan Shuen; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/s6hnd-80235", "eprint_id": 37376, "eprint_status": "archive", "datestamp": "2023-08-19 14:31:13", "lastmod": "2023-10-23 17:24:42", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pieper-Ursula", "name": { "family": "Pieper", "given": "Ursula" } }, { "id": "Schlessinger-Avner", "name": { "family": "Schlessinger", "given": "Avner" } }, { "id": "Kloppman-Edda", "name": { "family": "Kloppmann", "given": "Edda" } }, { "id": "Chang-Geoffrey-A", "name": { "family": "Chang", "given": "Geoffrey A." } }, { "id": "Chou-James-J", "name": { "family": "Chou", "given": "James J." } }, { "id": "Dumont-Mark-E", "name": { "family": "Dumont", "given": "Mark E." } }, { "id": "Fox-Brian-G", "name": { "family": "Fox", "given": "Brian G." } }, { "id": "Fromme-Petra", "name": { "family": "Fromme", "given": "Petra" } }, { "id": "Hendrickson-Wayne-A", "name": { "family": "Hendrickson", "given": "Wayne A." } }, { "id": "Malkowski-Michael-G", "name": { "family": "Malkowski", "given": "Michael G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Stokes-David-L", "name": { "family": "Stokes", "given": "David L." } }, { "id": "Stowell-Michael-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Wiener-Michael-C", "name": { "family": "Wiener", "given": "Michael C." } }, { "id": "Rost-Burkhard", "name": { "family": "Rost", "given": "Burkhard" } }, { "id": "Stroud-Robert-M", "name": { "family": "Stroud", "given": "Robert M." } }, { "id": "Stevens-Raymond-C", "name": { "family": "Stevens", "given": "Raymond C." } }, { "id": "Sali-Andrej", "name": { "family": "Sali", "given": "Andrej" } } ] }, "title": "Coordinating the impact of structural genomics on the human \u03b1-helical transmembrane proteome", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. \n\nReceived 16 August 2012; accepted 9 January 2013; published online 5 February 2013.\n\nWe thank I. Wilson, H. Berman, J. Chin and P. Preusch for critical comments on the manuscript. Research was supported by the US National Institutes of Health PSI:Biology grants U54 GM094662 (A.S., U.P.), U54 GM094618 (R.C.S.), U54 GM094625 (R.M.S., A.S., U.P.), U54 GM094584 (B.G.F.), U54\nGM094599 (P.F.), U54 GM094611 (M.C.W., M.E.D., M.G.M.), U54 GM094610 (G.A.C., D.C.R., M.H.B.S.), U54 GM094608 (J.J.C.), U54 GM095315 (W.A.H., B.R., E.K.) and U54 GM094598 (D.L.S.).\n\nAccepted Version - nihms460509.pdf
Supplemental Material - nsmb.2508-S1.pdf
", "abstract": "Given the recent successes in determining membrane-protein structures, we explore the tractability of determining representatives for the entire human membrane proteome. This proteome contains 2,925 unique integral \u03b1-helical transmembrane-domain sequences that cluster into 1,201 families sharing more than 25% sequence identity. Structures of 100 optimally selected targets would increase the fraction of modelable human \u03b1-helical transmembrane domains from 26% to 58%, providing structure and function information not otherwise available.", "date": "2013-02", "date_type": "published", "publication": "Nature Structural & Molecular Biology", "volume": "20", "number": "2", "publisher": "Nature Publishing Group", "pagerange": "135-138", "id_number": "CaltechAUTHORS:20130307-133554833", "issn": "1545-9985", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130307-133554833", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "U54 GM094662" }, { "agency": "NIH", "grant_number": "U54 GM094618" }, { "agency": "NIH", "grant_number": "U54 GM094625" }, { "agency": "NIH", "grant_number": "U54 GM094584" }, { "agency": "NIH", "grant_number": "U54 GM094599" }, { "agency": "NIH", "grant_number": "U54 GM094611" }, { "agency": "NIH", "grant_number": "U54 GM094610" }, { "agency": "NIH", "grant_number": "U54 GM094608" }, { "agency": "NIH", "grant_number": "U54 GM095315" }, { "agency": "NIH", "grant_number": "U54 GM094598" } ] }, "doi": "10.1038/nsmb.2508", "pmcid": "PMC3645303", "primary_object": { "basename": "nihms460509.pdf", "url": "https://authors.library.caltech.edu/records/s6hnd-80235/files/nihms460509.pdf" }, "related_objects": [ { "basename": "nsmb.2508-S1.pdf", "url": "https://authors.library.caltech.edu/records/s6hnd-80235/files/nsmb.2508-S1.pdf" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Pieper, Ursula; Schlessinger, Avner; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ckzp2-fz962", "eprint_id": 29486, "eprint_status": "archive", "datestamp": "2023-08-22 04:42:24", "lastmod": "2023-10-24 22:14:42", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bobyr-E", "name": { "family": "Bobyr", "given": "Elena" } }, { "id": "Lassila-J-K", "name": { "family": "Lassila", "given": "Jonathan K." } }, { "id": "Wiersma-Koch-H-I", "name": { "family": "Wiersma-Koch", "given": "Helen I." } }, { "id": "Fenn-T-D", "name": { "family": "Fenn", "given": "Timothy D." } }, { "id": "Lee-J-J", "name": { "family": "Lee", "given": "Jason J." } }, { "id": "Nikolic-Hughes-I", "name": { "family": "Nikolic-Hughes", "given": "Ivana" } }, { "id": "Hodgson-K-O", "name": { "family": "Hodgson", "given": "Keith O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Hedman-B", "name": { "family": "Hedman", "given": "Britt" } }, { "id": "Herschlag-D", "name": { "family": "Herschlag", "given": "Daniel" } } ] }, "title": "High-Resolution Analysis of Zn^2+ Coordination in the Alkaline Phosphatase Superfamily by EXAFS and X-ray Crystallography", "ispublished": "pub", "full_text_status": "public", "keywords": "x-ray absorption spectroscopy; crystal structure; nucleotide pyrophosphatase/phosphodiesterase; catalytic promiscuity; phosphoryl transfer", "note": "\u00a9 2011 Elsevier Ltd.\n\nReceived 17 August 2011; received in revised form 21 October 2011; accepted 24 October 2011. Available online\n28 October 2011.\n\nWe thank members of the Herschlag laboratory for helpful comments on the manuscript, Dr. Jun-yong Choe for assistance with diffraction data collection, Dr. Stefan Steinbacher for participating in the initial crystallographic refinement, Dr. Axel T. Brunger for the use of facilities for crystallographic refinement, and Jesse G. Zalatan for sharing unpublished NPP binding data. This work was supported by grants from the National Institutes of Health (NIH) to D.H. (GM64798), D.C.R., (GM045162), and K.O.H. (RR001209). J.K.L. was supported by an NIH postdoctoral fellowship (F32 GM080865). T.D.F.\nwas supported by the Universitywide AIDS Research Program of the University of California (F03-ST-216). Facilities used for x-ray crystallography in the laboratory of Axel T. Brunger were supported by Howard Hughes Medical Institute. Portions of this research were carried out at the SSRL, a Directorate of Stanford Linear Accelerator Center National\nAccelerator Laboratory and an Office of Science User Facility operated for the U.S. Department of\nEnergy Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the Department of Energy, Office of Biological and Environmental Research, and by the NIH, National Center for Research Resources, Biomedical Technology Program, and the National Institute of General Medical Sciences. The publication was partially supported by grant number 5 P41\nRR001209 from the National Center for Research Resources, a component of the NIH, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the NIH.\n\nAccepted Version - nihms340679.pdf
", "abstract": "Comparisons among evolutionarily related enzymes offer opportunities to reveal how structural differences produce different catalytic activities. Two structurally related enzymes, Escherichia coli alkaline phosphatase (AP) and\nXanthomonas axonopodis nucleotide pyrophosphatase/phosphodiesterase (NPP), have nearly identical binuclear Zn^2+ catalytic centers but show tremendous differential specificity for hydrolysis of phosphate monoesters or phosphate diesters. To determine if there are differences in Zn^2+ coordination in the two enzymes that might contribute to catalytic specificity, we analyzed both x-ray absorption spectroscopic and x-ray\ncrystallographic data. We report a 1.29-\u00c5 crystal structure of AP with bound phosphate, allowing evaluation of interactions at the AP metal site with high resolution. To make systematic comparisons between AP and NPP, we measured zinc extended x-ray absorption fine structure for AP and\nNPP in the free-enzyme forms, with AMP and inorganic phosphate groundstate analogs and with vanadate transition-state analogs. These studies yielded average zinc\u2013ligand distances in AP and NPP free-enzyme forms\nand ground-state analog forms that were identical within error, suggesting little difference in metal ion coordination among these forms. Upon binding of vanadate to both enzymes, small increases in average metal\u2013ligand distances were observed, consistent with an increased coordination number. Slightly longer increases were observed in NPP relative to AP, which could arise from subtle rearrangements of the active site or differences in the geometry of the bound vanadyl species. Overall, the\nresults suggest that the binuclear Zn^2+ catalytic site remains very similar between AP and NPP during the course of a reaction cycle.", "date": "2012-01-06", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "415", "number": "1", "publisher": "Elsevier", "pagerange": "102-117", "id_number": "CaltechAUTHORS:20120227-122308180", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120227-122308180", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM64798" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "NIH", "grant_number": "RR001209" }, { "agency": "NIH postdoctoral fellowship", "grant_number": "F32 GM080865" }, { "agency": "University of California Universitywide AIDS Research Program", "grant_number": "F03-ST-216" }, { "agency": "NIH", "grant_number": "5 P41 RR001209" } ] }, "doi": "10.1016/j.jmb.2011.10.040", "pmcid": "PMC3249517", "primary_object": { "basename": "nihms340679.pdf", "url": "https://authors.library.caltech.edu/records/ckzp2-fz962/files/nihms340679.pdf" }, "resource_type": "article", "pub_year": "2012", "author_list": "Bobyr, Elena; Lassila, Jonathan K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qq1vj-3cf08", "eprint_id": 29457, "eprint_status": "archive", "datestamp": "2023-08-22 04:36:44", "lastmod": "2023-10-24 22:12:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Johnson-E", "name": { "family": "Johnson", "given": "Eric" } }, { "id": "Nguyen-Phong-T", "name": { "family": "Nguyen", "given": "Phong T." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "Todd O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Inward facing conformations of the MetNI methionine ABC transporter: Implications for the mechanism of transinhibition", "ispublished": "pub", "full_text_status": "restricted", "keywords": "membrane protein structure; importers; ATP binding cassette; allosteric regulation", "note": "\u00a9 2011 The Protein Society. Received 24 September 2011; Revised 6 November 2011; Accepted 7 November 2011. Published online 16 November 2011. Additional Supporting Information may be found in the online version of this article. Grant sponsor: NIH; Grant number: GM045162. A Vietnam International Education Development scholarship to P.T.N. from the Vietnam Ministry of Education and Training scholarship is gratefully acknowledged. The authors thank the Gordon and Betty Moore Foundation and the Sanofi-Aventis Bioengineering\nResearch Program at Caltech for their generous support of the Molecular Observatory at Caltech. Portions of this research were carried out at\nthe Stanford Synchrotron Radiation Lightsource (SSRL), a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility\noperated for the U.S. Department of Energy Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the\nDOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program (P41RR001209), and the National Institute of General Medical Sciences. Coordinates and structure factors have been deposited in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics, with IDs 3TUI, 3TUJ, and 3TUZ for the CY5, DM, and CY5 SeMet soak structures,\nrespectively.", "abstract": "Two new crystal structures of the Escherichia coli high affinity methionine uptake ATP Binding Cassette (ABC) transporter MetNI, purified in the detergents cyclohexyl-pentyl-\u03b2-D-maltoside (CY5) and n-decyl-\u03b2-D-maltopyranoside (DM), have been solved in inward facing conformations to resolutions of 2.9 and 4.0 \u00c5, respectively. Compared to the previously reported 3.7 \u00c5 resolution structure of MetNI purified in n-dodecyl-\u03b2-D-maltopyranoside (DDM), the higher resolution of the CY5 data enabled significant improvements to the structural model in several regions, including corrections to the sequence registry, and identification of ADP in the nucleotide binding site. CY5 crystals soaked with selenomethionine established details of the methionine binding site in the C2 regulatory domain of the ABC subunit, including the displacement of the side chain of MetN residue methionine 301 by the exogenous ligand. When compared to the CY5 or DDM structures, the DM structure exhibits a significant repositioning of the dimeric C2 domains, including an unexpected register shift in the intermolecular \u03b2-sheet hydrogen bonding between monomers, and a narrowing of the nucleotide binding space. The immediate proximity of the exogenous methionine binding site to the conformationally variable dimeric interface provides an indication of how methionine binding to the regulatory domains might mediate the phenomenon of transinhibition.", "date": "2012-01", "date_type": "published", "publication": "Protein Science", "volume": "21", "number": "1", "publisher": "Wiley", "pagerange": "84-96", "id_number": "CaltechAUTHORS:20120224-110410533", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120224-110410533", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Sanofi-Aventis Bioengineering Research Program" }, { "agency": "Stanford Synchrotron Radiation Lightsource (SSRL)" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH" }, { "agency": "NCRR", "grant_number": "P41RR001209" }, { "agency": "National Institute of General Medical Sciences" } ] }, "doi": "10.1002/pro.765", "pmcid": "PMC3323783", "resource_type": "article", "pub_year": "2012", "author_list": "Johnson, Eric; Nguyen, Phong T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5hxc3-nk458", "eprint_id": 75653, "eprint_status": "archive", "datestamp": "2023-08-22 04:23:41", "lastmod": "2023-10-25 15:11:26", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Roy-R", "name": { "family": "Roy", "given": "Roopali" } }, { "id": "Dhawan-I-K", "name": { "family": "Dhawan", "given": "Ish K." } }, { "id": "Johnson-M-K", "name": { "family": "Johnson", "given": "Michael K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } } ] }, "title": "Aldehyde Ferredoxin Oxidoreductase", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "tungsten; tungsten-containing enzyme; pterin cofactor; iron-sulfur cluster; aldehyde oxidoreductase; ferredoxin; pyrococcus furiosus; hyperthermophile", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nPublished Online: 15 DEC 2011.\n\nResearch on tungstoenzymes carried out in the authors' laboratories was supported by grants from the Department of Energy, the National Science Foundation and the National Institutes of Health.", "abstract": "Aldehyde ferredoxin oxidoreductase (AOR) is a homodimer where each subunit contains a [4Fe\u20134S] cluster and a mononuclear tungsten atom coordinated by the dithioline groups of two pterin molecules. The two subunits of the dimer are bridged by a monomeric iron site. AOR is a member of a family of five closely related tungstoenzymes found in organisms that grow at high temperatures in marine volcanic vents. The enzyme catalyzes the two-electron oxidation of its aldehyde substrate to the corresponding acid with the concomitant reduction of ferredoxin, its physiological electron acceptor. The enzyme can oxidize a wide range of aliphatic and aromatic aldehydes. The most efficient substrates for AOR are acetaldehyde, isovaleraldehyde, phenylacetaldehyde, and indoleacetaldehyde, the aldehyde derivatives of some of the most common amino acids.", "date": "2011-12-15", "date_type": "published", "publisher": "Wiley", "place_of_pub": "Hoboken, NJ", "id_number": "CaltechAUTHORS:20170403-152926110", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170403-152926110", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NSF" }, { "agency": "NIH" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0607", "resource_type": "book_section", "pub_year": "2011", "author_list": "Roy, Roopali; Dhawan, Ish K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sx99r-07g72", "eprint_id": 75541, "eprint_status": "archive", "datestamp": "2023-08-22 04:23:20", "lastmod": "2023-10-25 15:07:44", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Hendrich-M-P", "name": { "family": "Hendrich", "given": "Michael P." } }, { "id": "Arciero-D-M", "name": { "family": "Arciero", "given": "David M." } }, { "id": "Hooper-A-B", "name": { "family": "Hooper", "given": "Alan B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Cytochrome c_(554)", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "cytochrome c554; biological nitrogen cycle; heme-proteins; electron transfer proteins; nitrification", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nPublished Online: 15 DEC 2011. \n\nThis article was originally published in the Handbook of Metalloproteins in 2006 by John Wiley & Sons, Ltd. \n\nSupported by NSF Research to ABH (# MCB-9316906) and NIH to DCR (GM45162).", "abstract": "Cytochrome c_(554) (cyt c_(554)) is a tetra-heme c-type cytochrome that participates in the nitrification pathway of Nitrosomonas europaea. In this process, cyt c_(554) functions as the electron acceptor from the enzyme hydroxylamine oxidoreductase that catalyzes the oxidation of hydroxylamine to nitrite. Cyt c_(554) is a predominantly \u03b1-helical protein with four covalently attached hemes. The four hemes are arranged in two pairs, such that the planes of the porphyrin rings are nearly parallel and overlapping at the edges. This type of heme-stacking has been observed in two other nitrogen cycle proteins: hydroxylamine oxidoreductase and cytochrome c nitrite reductase, an enzyme that catalyzes the reduction of nitrite to ammonia. The relatively unusual spectral properties of cyt c_(554) may reflect interactions between these pairs of stacked hemes.", "date": "2011-12-15", "date_type": "published", "publisher": "John Wiley and Sons, Inc.", "place_of_pub": "Hoboken, NJ", "pagerange": "Art. No. eibc0538", "id_number": "CaltechAUTHORS:20170330-105823002", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170330-105823002", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-9316906" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0538", "resource_type": "book_section", "pub_year": "2011", "author_list": "Iverson, Tina M.; Hendrich, Michael P.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jvmxy-4z657", "eprint_id": 86024, "eprint_status": "archive", "datestamp": "2023-08-22 04:24:17", "lastmod": "2023-10-18 19:11:45", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Hendrich-M-P", "name": { "family": "Hendrich", "given": "Michael P." } }, { "id": "Arciero-D-M", "name": { "family": "Arciero", "given": "David M." } }, { "id": "Hooper-A-B", "name": { "family": "Hooper", "given": "Alan B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Cytochrome c_(554)", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "cytochrome c_(554); biological nitrogen cycle; heme\u2010proteins; electron transfer proteins; nitrification", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nPublished Online: 15 December 2011. \n\nSupported by NSF Research to ABH (#MCB-9316906) and NIH to DCR (GM45162).", "abstract": "Cytochrome c_(554) (cyt c_(554)) is a tetra\u2010heme c\u2010type cytochrome that participates in the nitrification pathway of Nitrosomonas europaea. In this process, cyt c_(554) functions as the electron acceptor from the enzyme hydroxylamine oxidoreductase that catalyzes the oxidation of hydroxylamine to nitrite. Cyt c_(554) is a predominantly \u03b1\u2010helical protein with four covalently attached hemes. The four hemes are arranged in two pairs, such that the planes of the porphyrin rings are nearly parallel and overlapping at the edges. This type of heme\u2010stacking has been observed in two other nitrogen cycle proteins: hydroxylamine oxidoreductase and cytochrome c nitrite reductase, an enzyme that catalyzes the reduction of nitrite to ammonia. The relatively unusual spectral properties of cyt c_(554) may reflect interactions between these pairs of stacked hemes.", "date": "2011-12-15", "date_type": "published", "publisher": "Wiley", "place_of_pub": "Hoboken, NJ", "pagerange": "1-12", "id_number": "CaltechAUTHORS:20180424-134640337", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180424-134640337", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-9316906" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0538", "resource_type": "book_section", "pub_year": "2011", "author_list": "Iverson, Tina M.; Hendrich, Michael P.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pq0bd-hgj42", "eprint_id": 86013, "eprint_status": "archive", "datestamp": "2023-08-22 04:24:01", "lastmod": "2023-10-18 19:11:05", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Roy-R", "name": { "family": "Roy", "given": "Roopali" } }, { "id": "Dhawan-I-K", "name": { "family": "Dhawan", "given": "Ish K." } }, { "id": "Johnson-M-K", "name": { "family": "Johnson", "given": "Michael K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } } ] }, "title": "Formaldehyde Ferredoxin Oxidoreductase", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "tungsten; tungsten\u2010containing enzyme; formaldehyde oxidoreductase; iron\u2010sulfur cluster; pterin cofactor; pyrococcus furiosus; thermococcus litoralis; semialdehyde oxidation; hyperthermophile; ferredoxin", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nPublished Online: 15 December 2011. \n\nResearch on tungstoenzymes carried out in the authors' laboratories was supported by grants from the Department of Energy, the National Science Foundation and the National Institutes of Health.", "abstract": "Formaldehyde ferredoxin oxidoreductase (FOR) is a homotetramer where each subunit contains a [4Fe\u20134S] cluster and a mononuclear tungsten atom coordinated by the dithioline groups of two pterin molecules. It is a member of a family of five closely related tungstoenzymes found in organisms that grow at high temperatures in marine volcanic vents. FOR catalyzes the two\u2010electron oxidation of its aldehyde substrate to the corresponding acid with the concomitant reduction of ferredoxin, its physiological electron acceptor. FOR oxidizes short chain C1\u2010C4 aldehydes as substrates but has the highest affinity for C_4\u2010C_6 di\u2010 and semialdehydes. The enzyme is proposed to have a role in peptide metabolism.", "date": "2011-12-15", "date_type": "published", "publisher": "Wiley", "place_of_pub": "Hoboken, NJ", "pagerange": "1-12", "id_number": "CaltechAUTHORS:20180423-113156107", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180423-113156107", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NSF" }, { "agency": "NIH" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0606", "resource_type": "book_section", "pub_year": "2011", "author_list": "Roy, Roopali; Dhawan, Ish K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hanew-fxw25", "eprint_id": 75652, "eprint_status": "archive", "datestamp": "2023-08-22 04:23:32", "lastmod": "2023-10-25 15:11:21", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Roy-R", "name": { "family": "Roy", "given": "Roopali" } }, { "id": "Dhawan-I-K", "name": { "family": "Dhawan", "given": "Ish K." } }, { "id": "Johnson-M-K", "name": { "family": "Johnson", "given": "Michael K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } } ] }, "title": "Formaldehyde Ferredoxin Oxidoreductase", "ispublished": "unpub", "full_text_status": "public", "keywords": "tungsten; tungsten-containing enzyme; formaldehyde oxidoreductase; iron-sulfur cluster; pterin cofactor; pyrococcus furiosus; thermococcus litoralis; semialdehyde oxidation; hyperthermophile; ferredoxin", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nPublished Online: 15 DEC 2011. \n\nResearch on tungstoenzymes carried out in the authors' laboratories was supported by grants from the Department of Energy, the National Science Foundation and the National Institutes of Health.", "abstract": "Formaldehyde ferredoxin oxidoreductase (FOR) is a homotetramer where each subunit contains a [4Fe\u20134S] cluster and a mononuclear tungsten atom coordinated by the dithioline groups of two pterin molecules. It is a member of a family of five closely related tungstoenzymes found in organisms that grow at high temperatures in marine volcanic vents. FOR catalyzes the two-electron oxidation of its aldehyde substrate to the corresponding acid with the concomitant reduction of ferredoxin, its physiological electron acceptor. FOR oxidizes short chain C_1-C_4 aldehydes as substrates but has the highest affinity for C_4-C_6 di- and semialdehydes. The enzyme is proposed to have a role in peptide metabolism.", "date": "2011-12-15", "date_type": "published", "publisher": "Wiley", "place_of_pub": "Hoboken, NJ", "id_number": "CaltechAUTHORS:20170403-151722541", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170403-151722541", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NSF" }, { "agency": "NIH" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0606", "resource_type": "book_section", "pub_year": "2011", "author_list": "Roy, Roopali; Dhawan, Ish K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/59gt9-hc333", "eprint_id": 75542, "eprint_status": "archive", "datestamp": "2023-08-22 04:23:28", "lastmod": "2023-10-25 15:07:51", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schmid-B", "name": { "family": "Schmid", "given": "Benedikt" } }, { "id": "Chiu-Hsiu-Ju", "name": { "family": "Chiu", "given": "Hsiu-Ju" } }, { "id": "Ramakrishnan-V", "name": { "family": "Ramakrishnan", "given": "Vijay" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "nitrogenase; biological nitrogen fixation; biological nitrogen cycle; electron-transfer proteins; nucleotide binding proteins; iron-sulfur proteins", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nResearch on nitrogenase carried out in the author's laboratories was supported by a grant from the National Institutes of Health.", "abstract": "Nitrogenase catalyzes the enzymatic reduction of atmospheric dinitrogen to ammonia during the process of biological nitrogen fixation. Nitrogenase consists of two component metalloproteins, the iron (Fe-) protein and the molybdenum-iron (MoFe-) protein, that together mediate the ATP-hydrolysis\u2013dependent reduction of substrates to products. Crystallographic studies have established the structures of the component proteins and the associated complex metallocenters of nitrogenase, including the iron-molybdenum cofactor that provides the active site for substrate reduction and the P-cluster that participates in electron transfer between the Fe-protein and MoFe-protein. Striking parallels are evident in the interaction of the nucleotides with the Fe-protein and with a broad class of nucleotide-binding proteins involved in signal and energy transduction processes. Together with kinetic, spectroscopic, and synthetic model compound studies, these structures provide a framework for addressing the mechanism of substrate reduction by nitrogenase.", "date": "2011-12-15", "date_type": "published", "publisher": "John Wiley and Sons, Inc.", "place_of_pub": "Hoboken, NJ", "pagerange": "Art. No. eibc0601", "id_number": "CaltechAUTHORS:20170330-111026101", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170330-111026101", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0601", "resource_type": "book_section", "pub_year": "2011", "author_list": "Schmid, Benedikt; Chiu, Hsiu-Ju; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rt3k6-nny83", "eprint_id": 85992, "eprint_status": "archive", "datestamp": "2023-08-22 04:23:52", "lastmod": "2023-10-18 19:09:50", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schmid-B", "name": { "family": "Schmid", "given": "Benedikt" } }, { "id": "Chiu-Hsiu-Ju", "name": { "family": "Chiu", "given": "Hsiu-Ju" } }, { "id": "Ramakrishnan-V", "name": { "family": "Ramakrishnan", "given": "Vijay" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "nitrogenase; biological nitrogen fixation; biological nitrogen cycle; electron\u2010transfer proteins; nucleotide binding proteins; iron\u2010sulfur proteins", "note": "\u00a9 2011 John Wiley & Sons, Ltd. \n\nThis article was originally published in the Handbook of Metalloproteins in 2006 by John Wiley & Sons, Ltd. \n\nPublished Online: 15 December 2011. \n\nResearch on nitrogenase carried out in the author's laboratories was supported by a grant from the National Institutes of Health.", "abstract": "Nitrogenase catalyzes the enzymatic reduction of atmospheric dinitrogen to ammonia during the process of biological nitrogen fixation. Nitrogenase consists of two component metalloproteins, the iron (Fe\u2010) protein and the molybdenum\u2010iron (MoFe\u2010) protein, that together mediate the ATP\u2010hydrolysis\u2013dependent reduction of substrates to products. Crystallographic studies have established the structures of the component proteins and the associated complex metallocenters of nitrogenase, including the iron\u2010molybdenum cofactor that provides the active site for substrate reduction and the P\u2010cluster that participates in electron transfer between the Fe\u2010protein and MoFe\u2010protein. Striking parallels are evident in the interaction of the nucleotides with the Fe\u2010protein and with a broad class of nucleotide\u2010binding proteins involved in signal and energy transduction processes. Together with kinetic, spectroscopic, and synthetic model compound studies, these structures provide a framework for addressing the mechanism of substrate reduction by nitrogenase.", "date": "2011-12-15", "date_type": "published", "publisher": "Wiley", "place_of_pub": "Hoboken, NJ", "pagerange": "1-12", "id_number": "CaltechAUTHORS:20180420-155706178", "isbn": "9781119951438", "book_title": "Encyclopedia of Inorganic and Bioinorganic Chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180420-155706178", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" } ] }, "contributors": { "items": [ { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } } ] }, "doi": "10.1002/9781119951438.eibc0601", "resource_type": "book_section", "pub_year": "2011", "author_list": "Schmid, Benedikt; Chiu, Hsiu-Ju; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qf2gn-sed35", "eprint_id": 28340, "eprint_status": "archive", "datestamp": "2023-08-19 08:41:02", "lastmod": "2023-10-24 17:49:34", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Spatzal-T", "name": { "family": "Spatzal", "given": "Thomas" }, "orcid": "0000-0002-9136-5915" }, { "id": "Aksoyoglu-M", "name": { "family": "Aksoyoglu", "given": "M\u00fcge" } }, { "id": "Zhang-Limei", "name": { "family": "Zhang", "given": "Limei" } }, { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Schleicher-E", "name": { "family": "Schleicher", "given": "Erik" } }, { "id": "Weber-S", "name": { "family": "Weber", "given": "Stefan" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } } ] }, "title": "Evidence for Interstitial Carbon in Nitrogenase FeMo Cofactor", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2011 American Association for the Advancement of Science. Received 15 September 2011; accepted 19 October 2011. We thank the staff at Swiss Light Source, Villigen, Switzerland, and S. M. Consiglio for assistance with the calculations. The work was supported by Deutsche Forschungsgemeinschaft (grants Ei-520/7 to\nO.E., An-676/1 to S.L.A.A., and IRTG 1478), Natural\nSciences and Engineering Research Council of Canada\npostdoctoral fellowship to L.Z., NIH (grant GM45162 to\nD.C.R.), and HHMI (to D.C.R.). The structural model and\nstructure factors have been deposited with the Protein\nData Bank (accession code 3U7Q).\n\nAccepted Version - nihms349905.pdf
", "abstract": "The identity of the interstitial light atom in the center of the FeMo cofactor of nitrogenase has been enigmatic since its discovery. Atomic-resolution x-ray diffraction data and an electron spin echo envelope modulation (ESEEM) analysis now provide direct evidence that the ligand is a carbon species.", "date": "2011-11-18", "date_type": "published", "publication": "Science", "volume": "334", "number": "6058", "publisher": "American Association for the Advancement of Science", "pagerange": "940-940", "id_number": "CaltechAUTHORS:20111207-101914652", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111207-101914652", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "Ei-520/7" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "An-676/1" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "IRTG 1478" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "other_numbering_system": { "items": [ { "id": "3U7Q", "name": "Protein Bank accession code" } ] }, "doi": "10.1126/science.1214025", "pmcid": "PMC3268367", "primary_object": { "basename": "nihms349905.pdf", "url": "https://authors.library.caltech.edu/records/qf2gn-sed35/files/nihms349905.pdf" }, "resource_type": "article", "pub_year": "2011", "author_list": "Spatzal, Thomas; Aksoyoglu, M\u00fcge; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n6vdz-fq168", "eprint_id": 28434, "eprint_status": "archive", "datestamp": "2023-08-19 08:37:45", "lastmod": "2023-10-24 17:53:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tirado-Lee-L", "name": { "family": "Tirado-Lee", "given": "Laidamarie" } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Pinkett-H-W", "name": { "family": "Pinkett", "given": "Heather W." } } ] }, "title": "Classification of a Haemophilus influenzae ABC Transporter HI1470/71 through Its Cognate Molybdate Periplasmic Binding Protein, MoIA", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2011 Elsevier Ltd. Received 2 June 2011; revised 11 August 2011; Accepted 9 October 2011. Published: November 8, 2011. Available online 8 November 2011. We would like to thank Arabela Grigorescu, Ishwar Radhakrishnan, and Oded\nLewinson for useful discussions. We would also like to thank Keith MacRenaris\nand Rebecca Marvin for assistance with ICP-MS, Yongbo Zhang for assistance\nwith NMR titration studies, and Kaspar Locher for the initial cloning of\nHI1472. This work is based on research performed at SSRL, APS (21-ID-DG/\nF), funded by the Department of Energy. Research at Caltech was supported\nin part by NIH GM045162, by the Gordon and Betty Moore for their\nsupport of the Molecular Observatory, and by the James Irvine Foundation\nand United Negro College Fund-Merck for postdoctoral fellowships (to\nH.W.P.). This work was supported in part by a grant from ACS-IRG 93-037-\n15. Support for L.T.-L. was provided by NIH training Grant T32 GM008382.\n\nAccepted Version - nihms344071.pdf
", "abstract": "molA (HI1472) from H. influenzae encodes a periplasmic binding protein (PBP) that delivers substrate to the ABC transporter MolB_2C_2 (formerly HI1470/71). The structures of MolA with molybdate and tungstate in the binding pocket were solved to 1.6 and 1.7 \u00c5 resolution, respectively. The MolA-binding protein binds molybdate and tungstate, but not other oxyanions such as sulfate and phosphate, making it the first class III molybdate-binding protein structurally solved. The ~100 \u03bcM binding affinity for tungstate and molybdate is significantly lower than observed for the class II ModA molybdate-binding proteins that have nanomolar to low micromolar affinity for molybdate. The presence of two molybdate loci in H. influenzae suggests multiple transport systems for one substrate, with molABC constituting a low-affinity molybdate locus.", "date": "2011-11-09", "date_type": "published", "publication": "Structure", "volume": "19", "number": "11", "publisher": "Cell Press", "pagerange": "1701-1710", "id_number": "CaltechAUTHORS:20111213-082120248", "issn": "0969-2126", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111213-082120248", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "James Irvine Foundation" }, { "agency": "United Negro College Fund-Merck for postdoctoral fellowships" }, { "agency": "ACS-IRG", "grant_number": "93-037-15" }, { "agency": "NIH", "grant_number": "T32 GM008382" } ] }, "doi": "10.1016/j.str.2011.10.004", "pmcid": "PMC3258573", "primary_object": { "basename": "nihms344071.pdf", "url": "https://authors.library.caltech.edu/records/n6vdz-fq168/files/nihms344071.pdf" }, "resource_type": "article", "pub_year": "2011", "author_list": "Tirado-Lee, Laidamarie; Lee, Allen; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jcmjv-1gb94", "eprint_id": 27771, "eprint_status": "archive", "datestamp": "2023-08-19 08:21:34", "lastmod": "2023-10-24 17:24:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Haswell-E-S", "name": { "family": "Haswell", "given": "Elizabeth S." }, "orcid": "0000-0002-4246-065X" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Mechanosensitive Channels: What Can They Do and How Do They Do It?", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2011 Elsevier Ltd.\nAvailable online 11 October 2011.\n\nThe authors thank present and past members of their groups for dealing\nso constructively with tension, and Henry Lester for stimulating discussions.\nTheir research on mechanosensitive channels is supported by NIH grant GM084211.\n\nAccepted Version - nihms329278.pdf
", "abstract": "While mechanobiological processes employ diverse mechanisms, at their heart are force-induced perturbations in the structure and dynamics of molecules capable of triggering subsequent events. Among the best characterized force-sensing systems are bacterial mechanosensitive channels. These channels reflect an intimate coupling of protein conformation with the mechanics of the surrounding membrane; the membrane serves as an adaptable sensor that responds to an input of applied force and converts it into an output signal, interpreted for the cell by mechanosensitive channels. The cell can exploit this information in a number of ways: ensuring cellular viability in the presence of osmotic stress and perhaps also serving as a signal transducer for membrane tension or other functions. This review focuses on the bacterial mechanosensitive channels of large (MscL) and small (MscS) conductance and their eukaryotic homologs, with an emphasis on the outstanding issues surrounding the function and mechanism of this fascinating class of molecules.", "date": "2011-10-12", "date_type": "published", "publication": "Structure", "volume": "19", "number": "10", "publisher": "Cell Press", "pagerange": "1356-1369", "id_number": "CaltechAUTHORS:20111114-111309696", "issn": "0969-2126", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111114-111309696", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM084211" } ] }, "doi": "10.1016/j.str.2011.09.005", "pmcid": "PMC3203646", "primary_object": { "basename": "nihms329278.pdf", "url": "https://authors.library.caltech.edu/records/jcmjv-1gb94/files/nihms329278.pdf" }, "resource_type": "article", "pub_year": "2011", "author_list": "Haswell, Elizabeth S.; Phillips, Rob; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rx51s-5k918", "eprint_id": 22898, "eprint_status": "archive", "datestamp": "2023-08-22 01:58:18", "lastmod": "2023-10-23 17:19:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Gandhi-C-S", "name": { "family": "Gandhi", "given": "Chris S." } }, { "id": "Walton-T-A", "name": { "family": "Walton", "given": "Troy A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "OCAM: A new tool for studying the oligomeric diversity of MscL channels", "ispublished": "pub", "full_text_status": "public", "keywords": "subunit counting; oligomeric diversity; protein assembly; membrane protein; blue native PAGE; SEC-MALS; mechanosensitive channel", "note": "\u00a9 2010 The Protein Society.\nPublished by Wiley-Blackwell.\nReceived 2 September 2010; Revised 6 November 2010; Accepted 8 November 2010.\nArticle first published online: 28 Jan. 2011.\n\nThe authors thank Zhenfeng Liu for providing the\noriginal MscL constructs and discussion, Bil Clemons\nfor providing the sGFP construct, Heun Jin Lee for\ninsights into proteolysis, Nickie Chan for assistance\nwith BN-PAGE, and members of the Rees lab for helpful comments. We also graciously acknowledge\nWilliam Ockham for inspiration. D.C.R is an Investigator\nof the Howard Hughes Medical Institute.\n\nSupplemental Material - PRO_562_sm_suppinfo.doc
", "abstract": "We have developed a new technique to study the oligomeric state of proteins in solution. OCAM or Oligomer Characterization by Addition of Mass counts protein subunits by selectively shaving a protein mass tag added to a protein subunit via a short peptide linker. Cleavage of each mass tag reduces the total mass of the protein complex by a fixed amount. By performing limited proteolysis and separating the reaction products by size on a blue native PAGE gel, a ladder of reaction products corresponding to the number of subunits can be resolved. The pattern of bands may be used to distinguish the presence of a single homo-oligomer from a mixture of oligomeric states. We have applied OCAM to study the mechanosensitive channel of large conductance (MscL) and find that these proteins can exist in multiple oligomeric states ranging from tetramers up to possible hexamers. Our results demonstrate the existence of oligomeric forms of MscL not yet observed by X-ray crystallography or other techniques and that in some cases a single type of MscL subunit can assemble as a mixture of oligomeric states.", "date": "2011-02", "date_type": "published", "publication": "Protein Science", "volume": "20", "number": "2", "publisher": "Wiley", "pagerange": "313-326", "id_number": "CaltechAUTHORS:20110315-111219535", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110315-111219535", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM084211" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1002/pro.562", "pmcid": "PMC3048416", "primary_object": { "basename": "PRO_562_sm_suppinfo.doc", "url": "https://authors.library.caltech.edu/records/rx51s-5k918/files/PRO_562_sm_suppinfo.doc" }, "resource_type": "article", "pub_year": "2011", "author_list": "Gandhi, Chris S.; Walton, Troy A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/m50rz-1wh59", "eprint_id": 21934, "eprint_status": "archive", "datestamp": "2023-08-19 05:14:09", "lastmod": "2023-10-23 15:31:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Hu-Yilin", "name": { "family": "Hu", "given": "Yilin" } }, { "id": "Wiig-J-A", "name": { "family": "Wiig", "given": "Jared A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Ribbe-M-W", "name": { "family": "Ribbe", "given": "Markus W." } } ] }, "title": "Structure of Precursor-Bound NifEN: A Nitrogenase FeMo Cofactor Maturase/Insertase", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2011 American Association for the Advancement of Science.\n\nReceived for publication 25 August 2010. \nAccepted for publication 5 November 2010. \n\n\nThis work was supported by NIH grants GM-67626\n(M.W.R.) and GM-45162 (D.C.R.) D.C.R. is an\ninvestigator of the Howard Hughes Medical Institute.\nWe acknowledge the Gordon and Betty Moore Foundation\nfor support of the Molecular Observatory at California\nInstitute of Technology. Operations at the Stanford\nSynchrotron Radiation Lightsource are supported by the\nU.S. Department of Energy and NIH. The coordinates\nand structure factors have been deposited with the\nProtein Data Bank (PDB), accession number 3PDI.\n\nAccepted Version - nihms306799.pdf
", "abstract": "NifEN plays an essential role in the biosynthesis of the nitrogenase iron-molybdenum (FeMo) cofactor (M cluster). It is an \u03b1_2\u03b2_2 tetramer that is homologous to the catalytic molybdenum-iron (MoFe) protein (NifDK) component of nitrogenase. NifEN serves as a scaffold for the conversion of an iron-only precursor to a matured form of the M cluster before delivering the latter to its target location within NifDK. Here, we present the structure of the precursor-bound NifEN of Azotobacter vinelandii at 2.6 angstrom resolution. From a structural comparison of NifEN with des-M-cluster NifDK and holo NifDK, we propose similar pathways of cluster insertion for the homologous NifEN and NifDK proteins.", "date": "2011-01-07", "date_type": "published", "publication": "Science", "volume": "331", "number": "6013", "publisher": "American Association for the Advancement of Science", "pagerange": "91-94", "id_number": "CaltechAUTHORS:20110131-105156101", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110131-105156101", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-67626" }, { "agency": "NIH", "grant_number": "GM-45162" }, { "agency": "Gordon and Betty Moore Foundation" } ] }, "doi": "10.1126/science.1196954", "pmcid": "PMC3138709", "primary_object": { "basename": "nihms306799.pdf", "url": "https://authors.library.caltech.edu/records/m50rz-1wh59/files/nihms306799.pdf" }, "resource_type": "article", "pub_year": "2011", "author_list": "Kaiser, Jens T.; Hu, Yilin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3rxbq-qd564", "eprint_id": 18314, "eprint_status": "archive", "datestamp": "2023-08-21 23:40:24", "lastmod": "2023-10-20 16:06:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Liu-Zhenfeng", "name": { "family": "Liu", "given": "Zhenfeng" } }, { "id": "Walton-T-A", "name": { "family": "Walton", "given": "Troy A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A reported archaeal mechanosensitive channel is a structural homolog of MarR-like transcriptional regulators", "ispublished": "pub", "full_text_status": "restricted", "keywords": "mechanosensitive channel; multiple antibiotic resistance regulator; transcriptional regulator; winged helix-turn-helix motif", "note": "\u00a9 2010 The Protein Society.\nReceived: 27 December 2009; Revised: 23 January 2010; Accepted: 25 January 2010.\nThe authors thank A. Shih for cloning work, Y. Poon\nand J. Lai for protocols of osmotic downshock assay\nand lysogenizing MJF465 cells with kDE3, Y. Liu and\nM. Shahgholi for the mass spectrometry analysis, B.\nMartinac, H. Pinkett, and C. Gandhi for discussions, P.\nBlount for the MJF465 cells, and the staff at SSRL for\ntechnical support during data collection. The authors\nacknowledge the Gordon and Betty Moore Foundation\nfor support of the Molecular Observatory at Caltech.\nOperations at SSRL are supported by the U.S. Department\nof Energy and NIH. D. C. R. is an Investigator in\nthe Howard Hughes Medical Institute.", "abstract": "Several archaeal mechanosensitive (MS) channels have been reported, including one from Thermoplasma volcanium designated MscTV. Here, we report the crystal structure of MscTV at 1.6-\u00c5 resolution. Unexpectedly, MscTV was found to be a water-soluble protein exhibiting a winged helix-turn-helix (wHTH) motif, which is the signature of the MarR (multiple antibiotic resistance regulator) family of transcriptional regulators. A cell-based osmotic downshock functional assay demonstrated that MscTV was unable to protect a knockout strain of Escherichia coli from hypoosmotic shock, further indicating that it does not function as a MS channel. We propose this protein be renamed MLPTv for MarR-like protein from T. volcanium.", "date": "2010-04", "date_type": "published", "publication": "Protein Science", "volume": "19", "number": "4", "publisher": "Wiley", "pagerange": "808-814", "id_number": "CaltechAUTHORS:20100514-150930270", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100514-150930270", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM084211" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1002/pro.360", "pmcid": "PMC2867020", "resource_type": "article", "pub_year": "2010", "author_list": "Liu, Zhenfeng; Walton, Troy A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/193fc-a7h09", "eprint_id": 17906, "eprint_status": "archive", "datestamp": "2023-08-19 01:47:54", "lastmod": "2023-10-20 15:24:18", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A distinct mechanism for the ABC transporter BtuCD\u2013BtuF revealed by the dynamics of complex formation", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2010 Nature Publishing Group. \n\nReceived 9 June 2009; accepted 25 November 2009; published online 21 February 2010. \n\nWe thank H. Pinkett for insightful discussions and critical reading of the manuscript and J. Klein and J. Vielmetter for their help in the initial BiaCore experiments. The work was supported in part by US National Institutes of Health grant GM045162, by the Howard Hughes Medical Institute and by fellowships to O.L. from the Fulbright Foundation and the Jane Coffin Childs Memorial Fund for Medical Research.\nAuthor Contributions: \nA.T.L. and K.P.L. generated the original constructs used in this work; O.L. and D.C.R. designed the research; O.L. and A.T.L. performed the research; O.L., A.T.L., K.P.L. and D.C.R. analyzed the data; and O.L., K.P.L. and D.C.R. wrote the paper.\n\nAccepted Version - nihms-223277.pdf
Supplemental Material - nsmb.1770-S1.pdf
", "abstract": "ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a diverse array of substrates across cell membranes. We present here the dynamics of complex formation of three structurally characterized ABC transporters\u2014the BtuCD vitamin B_(12) importer and MetNI d/l-methionine importer from Escherichia coli and the Hi1470/1 metal-chelate importer from Haemophilus influenzae\u2014in complex with their cognate binding proteins. Similarly to other ABC importers, MetNI interacts with its binding protein with low affinity (K_d ~10^(\u22124) M). In contrast, BtuCD\u2013BtuF and Hi1470/1\u2013Hi1472 form stable, high-affinity complexes (K_d ~10^(\u221213) and 10^(\u22129) M, respectively). In BtuCD\u2013BtuF, vitamin B_(12) accelerates the complex dissociation rate ~10^7-fold, with ATP having an additional destabilizing effect. The findings presented here highlight substantial mechanistic differences between BtuCD\u2013BtuF, and likely Hi1470/1\u2013Hi1472, and the better-characterized maltose and related ABC transport systems, indicating that there is considerable mechanistic diversity within this large protein super-family.", "date": "2010-03", "date_type": "published", "publication": "Nature Structural & Molecular Biology", "volume": "17", "number": "3", "publisher": "Nature Publishing Group", "pagerange": "332-339", "id_number": "CaltechAUTHORS:20100408-134935074", "issn": "1545-9985", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100408-134935074", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Fulbright Foundation" }, { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" } ] }, "doi": "10.1038/nsmb.1770", "pmcid": "PMC2924745", "primary_object": { "basename": "nihms-223277.pdf", "url": "https://authors.library.caltech.edu/records/193fc-a7h09/files/nihms-223277.pdf" }, "related_objects": [ { "basename": "nsmb.1770-S1.pdf", "url": "https://authors.library.caltech.edu/records/193fc-a7h09/files/nsmb.1770-S1.pdf" } ], "resource_type": "article", "pub_year": "2010", "author_list": "Lewinson, Oded; Lee, Allen T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xtn56-gnp84", "eprint_id": 15800, "eprint_status": "archive", "datestamp": "2023-08-19 00:02:22", "lastmod": "2023-10-19 17:15:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Liu-Zhenfeng", "name": { "family": "Liu", "given": "Zhenfeng" } }, { "id": "Gandhi-C-S", "name": { "family": "Gandhi", "given": "Chris S." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of a tetrameric MscL in an expanded intermediate state", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2009 Nature Publishing Group. \n\nReceived 15 May 2009; Accepted 2 July 2009; Published online 23 August 2009. \n\nWe thank A. Shih for early cloning work, T. Walton for biochemical analysis, A. Lee for initial efforts on the MscL project, J. Choe for expression and purification protocols, O. Lewinson for manuscript reading, Y. Poon and J. Lai for treating MJF465 with lambdaDE3 and the osmotic down-shock assay protocol, J. Kaiser for suggestions on structure refinement, R. Phillips, E. Haswell and P. Pal for discussions, P. Blount for the MJF465 strain, and the staff at SSRL, the Advanced Light Source (ALS) and the Advanced Photon Source (APS) for technical support with crystal screening and data collection. We would like to acknowledge the Gordon and Betty Moore Foundation for support of the Molecular Observatory at Caltech. Operations at SSRL, ALS and APS are supported by the US Department of Energy and NIH. This work was supported in part by grants from the Howard Hughes Medical Institute and the National Institutes of Health (GM084211). C.S.G. was supported in part by postdoctoral fellowships from the National Institutes of Health and the Beckman Foundation. D.C.R. is an Investigator in the Howard Hughes Medical Institute. \n\nAuthor Contributions: Z.L. designed and performed the experiments in molecular biology, biochemistry, crystallography and the structure analysis. Z.L. and C.S.G. conducted the down-shock assays. C.S.G. was responsible for the protein reconstitution and electrophysiology. D.C.R. coordinated the project and contributed to the structure analysis. The manuscript was written by Z.L., C.S.G. and D.C.R. \n\nThe atomic coordinates and structure factors have been deposited at the Protein Data Bank with accession numbers 3HZQ. \n\nSupplementary information accompanies this paper.\n\nAccepted Version - nihms130657.pdf
Supplemental Material - nature08277-s1.pdf
Supplemental Material - nature08277-s2.mov
", "abstract": "The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation. In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassium-dependent (MscK) and mini (MscM) conductances. These channels act as 'emergency relief valves' protecting bacteria from lysis upon acute osmotic down-shock. Among them, MscL has been intensively studied since the original identification and characterization 15 years ago. MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a non-selective 3 nS conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 \u00c5 resolution of a pentameric MscL from Mycobacterium tuberculosis represents a closed-state or non-conducting conformation. MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative non-conductive expanded state and at least three sub-conducting states. Although our understanding of the closed and open states of MscL has been increasing, little is known about the structures of the intermediate states despite their importance in elucidating the complete gating process of MscL. Here we present the crystal structure of a carboxy-terminal truncation mutant (Delta95\u2013120) of MscL from Staphylococcus aureus (SaMscL(CDelta26)) at 3.8 \u00c5 resolution. Notably, SaMscL(CDelta26) forms a tetrameric channel with both transmembrane helices tilted away from the membrane normal at angles close to that inferred for the open state, probably corresponding to a non-conductive but partially expanded intermediate state.", "date": "2009-09-03", "date_type": "published", "publication": "Nature", "volume": "461", "number": "7260", "publisher": "Nature Publishing Group", "pagerange": "120-124", "id_number": "CaltechAUTHORS:20090911-153600479", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090911-153600479", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Department of Energy (DOE)" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM084211" }, { "agency": "Arnold and Mabel Beckman Foundation" } ] }, "doi": "10.1038/nature08277", "pmcid": "PMC2737600", "primary_object": { "basename": "nature08277-s2.mov", "url": "https://authors.library.caltech.edu/records/xtn56-gnp84/files/nature08277-s2.mov" }, "related_objects": [ { "basename": "nihms130657.pdf", "url": "https://authors.library.caltech.edu/records/xtn56-gnp84/files/nihms130657.pdf" }, { "basename": "nature08277-s1.pdf", "url": "https://authors.library.caltech.edu/records/xtn56-gnp84/files/nature08277-s1.pdf" } ], "resource_type": "article", "pub_year": "2009", "author_list": "Liu, Zhenfeng; Gandhi, Chris S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rxyd4-79548", "eprint_id": 14441, "eprint_status": "archive", "datestamp": "2023-08-21 21:03:54", "lastmod": "2023-10-18 17:59:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A P-type ATPase importer that discriminates between essential and toxic transition metals", "ispublished": "pub", "full_text_status": "public", "keywords": "membrane proteins; transition-metal homeostasis; heavy metal transporters; P-1B ATPases", "note": "\u00a9 2009 by the National Academy of Sciences. Freely available online through the PNAS open access option. \n\nContributed by Douglas C. Rees, January 26, 2009 (received for review October 15, 2008). http://dx.doi.org/10.1073/pnas.0900666106\nWe thank Nathan Dalleska and the Environmental Analysis\nCenter for assistance with the metal analyses. The work was supported in part\nby National Institutes of Health Grant GM045162, by the Howard Hughes Medical\nInstitute, and by fellowships to O.L. from the Fulbright Foundation and the Jane\nCoffin Childs Memorial Fund for Medical Research. \n\nAuthor contributions: O.L. and D.C.R. designed research; O.L. and A.T.L. performed research; O.L., A.T.L., and D.C.R. analyzed data; and O.L. and D.C.R. wrote the paper. \n\nThe authors declare no conflict of interest.\n\nPublished - Lewinson2009p1326P_Natl_Acad_Sci_Usa.pdf
", "abstract": "Transition metals, although being essential cofactors in many physiological processes, are toxic at elevated concentrations. Among the membrane-embedded transport proteins that maintain appropriate intracellular levels of transition metals are ATP-driven pumps belonging to the P-type ATPase superfamily. These metal transporters may be differentiated according to their substrate specificities, where the majority of pumps can extrude either silver and copper or zinc, cadmium, and lead. In the present report, we have established the substrate specificities of nine previously uncharacterized prokaryotic transition-metal P-type ATPases. We find that all of the newly identified exporters indeed fall into one of the two above-mentioned categories. In addition to these exporters, one importer, Pseudomonas aeruginosa Q9I147, was also identified. This protein, designated HmtA (heavy metal transporter A), exhibited a different substrate recognition profile from the exporters. In vivo metal susceptibility assays, intracellular metal measurements, and transport experiments all suggest that HmtA mediates the uptake of copper and zinc but not of silver, mercury, or cadmium. The substrate selectivity of this importer ensures the high-affinity uptake of essential metals, while avoiding intracellular contamination by their toxic counterparts.", "date": "2009-03-24", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "number": "12", "publisher": "National Academy of Sciences", "pagerange": "4677-4682", "id_number": "CaltechAUTHORS:20090624-100450865", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090624-100450865", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM045162" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Fulbright Foundation" }, { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" } ] }, "doi": "10.1073/pnas.0900666106", "pmcid": "PMC2651836", "primary_object": { "basename": "Lewinson2009p1326P_Natl_Acad_Sci_Usa.pdf", "url": "https://authors.library.caltech.edu/records/rxyd4-79548/files/Lewinson2009p1326P_Natl_Acad_Sci_Usa.pdf" }, "resource_type": "article", "pub_year": "2009", "author_list": "Lewinson, Oded; Lee, Allen T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0qyfn-h4m32", "eprint_id": 15846, "eprint_status": "archive", "datestamp": "2023-08-20 01:03:37", "lastmod": "2023-10-19 17:18:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Johnson-E", "name": { "family": "Johnson", "given": "Eric" } }, { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } } ] }, "title": "ABC transporters: the power to change", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2009 Nature Publishing Group.\n\nWe thank A.T. Lee and J.B. Howard for discussions and their\nlong-term contributions to our research in this area. The support\nof the Fulbright Foundation and Jane Coffin Childs\nMemorial Funds for Medical Research (O.L.) and National\nInstitutes of Health grant GM45162 (D.C.R) is gratefully\nacknowledged.\n\nAccepted Version - nihms177334.pdf
Supplemental Material - Rees2009p9610.1038nrm2646_supp.pdf
Supplemental Material - Rees2009p9610.1038nrm2646_supp_2.pdf
Supplemental Material - Rees2009p9610.1038nrm2646_supp_3.pdf
", "abstract": "ATP-binding cassette (ABC) transporters constitute a ubiquitous superfamily of integral membrane proteins that are responsible for the ATP-powered translocation of many substrates across membranes. The highly conserved ABC domains of ABC transporters provide the nucleotide-dependent engine that drives transport. By contrast, the transmembrane domains that create the translocation pathway are more variable. Recent structural advances with prokaryotic ABC transporters have provided a qualitative molecular framework for deciphering the transport cycle. An important goal is to develop quantitative models that detail the kinetic and molecular mechanisms by which ABC transporters couple the binding and hydrolysis of ATP to substrate translocation.", "date": "2009-03", "date_type": "published", "publication": "Nature Reviews. Molecular Cell Biology", "volume": "10", "number": "3", "publisher": "Nature Publishing Group", "pagerange": "218-227", "id_number": "CaltechAUTHORS:20090915-075659915", "issn": "1471-0072", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090915-075659915", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Fulbright Foundation" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Jane Coffin Childs Memorial Funds for Medical Research" } ] }, "doi": "10.1038/nrm2646", "pmcid": "PMC2830722", "primary_object": { "basename": "Rees2009p9610.1038nrm2646_supp.pdf", "url": "https://authors.library.caltech.edu/records/0qyfn-h4m32/files/Rees2009p9610.1038nrm2646_supp.pdf" }, "related_objects": [ { "basename": "Rees2009p9610.1038nrm2646_supp_2.pdf", "url": "https://authors.library.caltech.edu/records/0qyfn-h4m32/files/Rees2009p9610.1038nrm2646_supp_2.pdf" }, { "basename": "Rees2009p9610.1038nrm2646_supp_3.pdf", "url": "https://authors.library.caltech.edu/records/0qyfn-h4m32/files/Rees2009p9610.1038nrm2646_supp_3.pdf" }, { "basename": "nihms177334.pdf", "url": "https://authors.library.caltech.edu/records/0qyfn-h4m32/files/nihms177334.pdf" } ], "resource_type": "article", "pub_year": "2009", "author_list": "Rees, Douglas C.; Johnson, Eric; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/scv7e-ffk92", "eprint_id": 14048, "eprint_status": "archive", "datestamp": "2023-08-21 20:51:47", "lastmod": "2023-10-18 16:04:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rice-A-E", "name": { "family": "Rice", "given": "Adrian E." } }, { "id": "Mendez-M-J", "name": { "family": "Mendez", "given": "Michael J." } }, { "id": "Hokanson-C-A", "name": { "family": "Hokanson", "given": "Craig A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990" } ] }, "title": "Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter", "ispublished": "pub", "full_text_status": "public", "keywords": "ferroportin; hemochromatosis; hepcidin; membrane protein; live-cell imaging", "note": "\u00a9 2008 Elsevier Ltd.\nReceived 16 October 2008; revised 3 December 2008; accepted 22 December 2008. Edited by J. Bowie. Available online 3 January 2009. \nThis work was supported by the National\nInstitutes of Health through grant 1R01 DK60770-\n01 (to P.J.B.) and a National Science Foundation\nGraduate Research Fellowship (A.E.R.). We thank\nmembers of the Bjorkman laboratory for critical\nreading of the manuscript and the Caltech Protein\nExpression Center for virus construction and high\ntiter virus production.\n\nAccepted Version - nihms99826.pdf
", "abstract": "Ferroportin is a multipass membrane protein that serves as an iron exporter in many vertebrate cell types. Ferroportin-mediated iron export is controlled by the hormone hepcidin, which binds ferroportin, causing its internalization and degradation. Mutations in ferroportin cause a form of the iron overload hereditary disease hemochromatosis. Relatively little is known about ferroportin's properties or the mechanism by which mutations cause disease. In this study, we expressed and purified human ferroportin to characterize its biochemical/biophysical properties in solution and conducted cell biological studies in mammalian cells. We found that purified detergent-solubilized ferroportin is a well-folded monomer that binds hepcidin. In cell membranes, the N- and C-termini were both cytosolic, implying an even number of transmembrane regions, and ferroportin was mainly localized to the plasma membrane. Hepcidin addition resulted in a redistribution of ferroportin to intracellular compartments that labeled with early endosomal and lysosomal, but not Golgi, markers and that trafficked along microtubules. An analysis of 16 disease-related ferroportin mutants revealed that all were expressed and trafficked to the plasma membrane but that some were resistant to hepcidin-induced internalization. The characterizations reported here form a basis upon which models for ferroportin's role in regulating iron homeostasis in health and disease can be interpreted.", "date": "2009-02-27", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "386", "number": "3", "publisher": "Elsevier", "pagerange": "717-732", "id_number": "CaltechAUTHORS:20090422-143224842", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090422-143224842", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "1R01 DK6077001" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "doi": "10.1016/j.jmb.2008.12.063", "pmcid": "PMC2677177", "primary_object": { "basename": "nihms99826.pdf", "url": "https://authors.library.caltech.edu/records/scv7e-ffk92/files/nihms99826.pdf" }, "resource_type": "article", "pub_year": "2009", "author_list": "Rice, Adrian E.; Mendez, Michael J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/a7gnt-awq69", "eprint_id": 51626, "eprint_status": "archive", "datestamp": "2023-08-19 23:32:27", "lastmod": "2023-10-18 16:55:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Gandhi-C-S", "name": { "family": "Gandhi", "given": "Chris S." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Opening the Molecular Floodgates", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2008 American Association for the Advancement of Science.\n\nC.S.G. is supported by postdoctoral fellowships from the\nNIH and the Beckman Foundation.", "abstract": "Structural studies reveal how mechanosensitive channels respond to membrane tension.", "date": "2008-08-29", "date_type": "published", "publication": "Science", "volume": "321", "number": "5893", "publisher": "American Association for the Advancement of Science", "pagerange": "1166-1167", "id_number": "CaltechAUTHORS:20141112-081834738", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141112-081834738", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Arnold and Mabel Beckman Foundation" } ] }, "doi": "10.1126/science.1162963", "resource_type": "article", "pub_year": "2008", "author_list": "Gandhi, Chris S. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4j9v0-65r81", "eprint_id": 13510, "eprint_status": "archive", "datestamp": "2023-08-19 23:22:06", "lastmod": "2023-10-17 23:57:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "von-Heijne-G", "name": { "family": "von Heijne", "given": "Gunnar" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas" }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Membranes: reading between the lines", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2008 Elsevier Ltd.\nAvailable online 12th August 2008.", "abstract": "Membranes are remarkable entities; only ~40\u00c5 thick, they maintain the territorial integrity of a cell or organelle while regulating the flow of matter, information and energy between the interior and the external environment. The lipids and proteins that dominate the composition of membranes exhibit a characteristic architecture in which the lipids adopt a bilayer arrangement penetrated by integral membrane proteins [1]. In the common shorthand representation for this organization, the membrane bilayer is represented by two parallel lines with ellipsoidal membrane proteins embedded in a nonpolar continuum. While this depiction is obviously understood as a cartoon version of reality, it does convey a misleading impression of order in a biological membrane that belies the inherent compositional, structural and dynamic complexities of this system. Even for the simplest case of a bilayer composed of a single lipid type, a sharp interface does not exist between the lipid bilayer and surrounding aqueous solution, but rather there are substantial displacements of headgroups from the average plane, and the aliphatic chains in the bilayer interior are disordered owing to low torsional angle barriers and the steric consequences of cis-double bounds [[2], [3] and [4]]. The associated packing defects even allow polar compounds to penetrate into the membrane interior; as one consequence, water has an appreciable bilayer permeability [5]. The picture that emerges from such studies is that the biologically relevant fluid phase of membranes is highly dynamic, and the time-averaged structure can only be defined probabilistically.", "date": "2008-08", "date_type": "published", "publication": "Current Opinion in Structural Biology", "volume": "18", "number": "4", "publisher": "Elsevier", "pagerange": "403-405", "id_number": "CaltechAUTHORS:HEIcosb08", "issn": "0959-440X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:HEIcosb08", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1016/j.sbi.2008.06.003", "resource_type": "article", "pub_year": "2008", "author_list": "von Heijne, Gunnar and Rees, Douglas" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z6aq1-7hj26", "eprint_id": 51927, "eprint_status": "archive", "datestamp": "2023-08-19 23:11:28", "lastmod": "2023-10-18 18:42:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kadaba-N-S", "name": { "family": "Kadaba", "given": "Neena S." } }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Johnson-E", "name": { "family": "Johnson", "given": "Eric" } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2008 American Association for the Advancement of Science.\n\n18 March 2008; Accepted 10 June 2008.\n\nWe thank H. Pinkett, Z. Liu, O. Lewinson, L. Thompson, D. Tirrell, and J. B. Howard for helpful discussions and the\nstaffs of the Stanford Synchrotron Radiation Laboratory (SSRL) and the Advanced Light Source (ALS) for their assistance during crystal screening and data collection. This work was supported in part by NIH grant GM45162. We would like to acknowledge the Gordon and Betty Moore Foundation for support of the Molecular Observatory at Caltech. Operations at SSRL and ALS are supported by the U.S. Department of Energy and NIH. Coordinates and structure factors for MetNI and the MetN-C2 domain have been deposited in the Protein Data Bank (www.rcsb.org/pdb) (38) with the identification numbers 3DHW and 3DHX, respectively.\n\nAccepted Version - nihms-64174.pdf
Supplemental Material - Kadaba.SOM.pdf
", "abstract": "The crystal structure of the high-affinity Escherichia coli MetNI methionine uptake transporter, a member of the adenosine triphosphate (ATP)\u2013binding cassette (ABC) family, has been solved to 3.7 angstrom resolution. The overall architecture of MetNI reveals two copies of the adenosine triphosphatase (ATPase) MetN in complex with two copies of the transmembrane domain MetI, with the transporter adopting an inward-facing conformation exhibiting widely separated nucleotide binding domains. Each MetI subunit is organized around a core of five transmembrane helices that correspond to a subset of the helices observed in the larger membrane-spanning subunits of the molybdate (ModBC) and maltose (MalFGK) ABC transporters. In addition to the conserved nucleotide binding domain of the ABC family, MetN contains a carboxyl-terminal extension with a ferredoxin-like fold previously assigned to a conserved family of regulatory ligand-binding domains. These domains separate the nucleotide binding domains and would interfere with their association required for ATP binding and hydrolysis. Methionine binds to the dimerized carboxyl-terminal domain and is shown to inhibit ATPase activity. These observations are consistent with an allosteric regulatory mechanism operating at the level of transport activity, where increased intracellular levels of the transported ligand stabilize an inward-facing, ATPase-inactive state of MetNI to inhibit further ligand translocation into the cell.", "date": "2008-07-11", "date_type": "published", "publication": "Science", "volume": "321", "number": "5886", "publisher": "American Association for the Advancement of Science", "pagerange": "250-253", "id_number": "CaltechAUTHORS:20141118-161003885", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141118-161003885", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1126/science.1157987", "pmcid": "PMC2527972", "primary_object": { "basename": "Kadaba.SOM.pdf", "url": "https://authors.library.caltech.edu/records/z6aq1-7hj26/files/Kadaba.SOM.pdf" }, "related_objects": [ { "basename": "nihms-64174.pdf", "url": "https://authors.library.caltech.edu/records/z6aq1-7hj26/files/nihms-64174.pdf" } ], "resource_type": "article", "pub_year": "2008", "author_list": "Kadaba, Neena S.; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p5s2k-chm64", "eprint_id": 52777, "eprint_status": "archive", "datestamp": "2023-08-22 11:20:36", "lastmod": "2023-10-18 21:04:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lewinson-O", "name": { "family": "Lewinson", "given": "Oded" } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Funnel Approach to the Precrystallization Production of Membrane Proteins", "ispublished": "pub", "full_text_status": "public", "keywords": "membrane protein; crystallization; P-type ATPase", "note": "\u00a9 2007 Elsevier Ltd. All rights reserved.\n\nReceived 23 September 2007; received in revised form\n20 December 2007; accepted 21 December 2007\n\nThe authors would like to thank members of the Rees group for their help in the preparation of this manuscript. We thank Dietrich H. Nies for the generous gift of the plasmid DNA of R. metallidurans genes; Chris Rensing for strains W3110 and GG48; David B. Wilson for the plasmid DNA of Lactobacillus plantarum mntA; B. Sarkar for the plasmid\nDNA of Cu(6)-ZntA and Cu(1\u20136)\u2013zntA; Bharati Mitra for E. coli zntA; and Gianluca Quintini for H. pylori CadA. This work was supported, in part, by grants from the Fulbright Foundation and the Jane Coffin Childs Memorial Fund for Medical Research to O.L.\n\nAccepted Version - nihms43390.pdf
", "abstract": "Challenges in the production of integral membrane proteins for structural studies include low expression levels, incorrect membrane insertion, aggregation and instability. In this report, we describe a \"funnel approach\" to overcoming these difficulties and demonstrate its efficacy in a case study of 36 prokaryotic P-type transporters. A diverse ensemble of modified constructs is generated and tested for expression in Escherichia coli, membrane localization, detergent extraction, and homogeneity. High-throughput methodologies are implemented throughout the process to facilitate identification of promising targets. We find that the choice of promoter, the choice of source organism providing the cloned gene, and, most importantly, the position of the affinity tag have a great effect on successful production. The latter had pronounced effects at all tested levels, from expression levels observed in whole cells to the extent of membrane\ninsertion, and even on protein function. Following the initial streamlined screening, we were able to fine-tune and produce 9 of the 36 targets as materials suitable for crystallization or other structural studies.", "date": "2008-03-14", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "377", "number": "1", "publisher": "Elsevier", "pagerange": "62-73", "id_number": "CaltechAUTHORS:20141212-143814641", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-143814641", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Fulbright Foundation" }, { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" } ] }, "doi": "10.1016/j.jmb.2007.12.059", "pmcid": "PMC2362151", "primary_object": { "basename": "nihms43390.pdf", "url": "https://authors.library.caltech.edu/records/p5s2k-chm64/files/nihms43390.pdf" }, "resource_type": "article", "pub_year": "2008", "author_list": "Lewinson, Oded; Lee, Allen T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/egrh8-8g488", "eprint_id": 52778, "eprint_status": "archive", "datestamp": "2023-08-19 19:38:25", "lastmod": "2023-10-18 21:04:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Dobbek-H", "name": { "family": "Dobbek", "given": "Holger" } }, { "id": "Meyer-J", "name": { "family": "Meyer", "given": "Jacques" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Assignment of Individual Metal Redox States in a Metalloprotein by Crystallographic Refinement at Multiple X-ray Wavelengths", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 American Chemical Society\n\nReceived October 23, 2006\n\nDiffraction data were collected at SSRL, Stanford, and EMBL/DESY, Hamburg, Germany. This work was supported in part by EMBO YIP (O.E.), DFG (O.E., S.L.A.A.), CNRS and UJF (J.M.), and by NIH Grant GM45162 (D.C.R.).\n\nAccepted Version - nihms61980.pdf
Supplemental Material - ja067562osi20061023_065527.pdf
", "abstract": "A method is presented to derive anomalous scattering contributions for individual atoms within a protein crystal by collecting several sets of diffraction data at energies spread along an X-ray absorption edge of the element in question. The method has been applied to a [2Fe:2S] ferredoxin model system with localized charges in the reduced state of the iron\u2212sulfur cluster. The analysis shows that upon reduction the electron resides at the iron atom closer to the protein surface. The technique should be sufficiently sensitive for more complex clusters with noninteger redox states and is generally applicable given that crystals are available.", "date": "2007-02-02", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "129", "number": "8", "publisher": "American Chemical Society", "pagerange": "2210-2211", "id_number": "CaltechAUTHORS:20141212-144040144", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-144040144", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "European Molecular Biology Organization (EMBO)" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)" }, { "agency": "Centre National de la Recherche Scientifique (CNRS)" }, { "agency": "UJF" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1021/ja067562o", "pmcid": "PMC2527600", "primary_object": { "basename": "nihms61980.pdf", "url": "https://authors.library.caltech.edu/records/egrh8-8g488/files/nihms61980.pdf" }, "related_objects": [ { "basename": "ja067562osi20061023_065527.pdf", "url": "https://authors.library.caltech.edu/records/egrh8-8g488/files/ja067562osi20061023_065527.pdf" } ], "resource_type": "article", "pub_year": "2007", "author_list": "Einsle, Oliver; Andrade, Susana L. A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hsvex-vc439", "eprint_id": 51627, "eprint_status": "archive", "datestamp": "2023-08-19 19:33:25", "lastmod": "2023-10-18 16:55:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pinkett-H-W", "name": { "family": "Pinkett", "given": "H. W." } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "A. T." } }, { "id": "Lum-P", "name": { "family": "Lum", "given": "P." } }, { "id": "Locher-K-P", "name": { "family": "Locher", "given": "K. P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "An Inward-Facing Conformation of a Putative Metal-Chelate\u2013Type ABC Transporter", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 American Association for the Advancement of Science.\n\nReceived 4 August 2006; accepted 30 November 2006\nPublished online 7 December 2006.\n\nWe thank L. Thomas and J. Kaiser for their contributions\nto the structure determination, N. Kadaba and\nJ. B. Howard for discussions, and the staff of the Stanford\nSynchrotron Radiation Laboratory (SSRL) for their\nassistance during crystal screening and data collection.\nThis work was supported in part by NIH grant GM45162.\nWe acknowledge support for fellowships from the James\nIrvine Foundation (H.W.P.) and NIH (P.L.), the Vallee\nFoundation (D.C.R.), the Parsons Foundation for\ncomputational resources, and the Gordon and Betty\nMoore Foundation for support of the Molecular\nObservatory at Caltech. SSRL is supported by DOE and\nNIH. Coordinates have been deposited in the Protein\nData Bank (PDB) [www.rcsb.org/pdb; (31)] as entry 2NQ2\nfor release upon publication.\n\nSupplemental Material - Pinkett-SOM.pdf
", "abstract": "The crystal structure of a putative metal-chelate\u2013type adenosine triphosphate (ATP)\u2013binding cassette (ABC) transporter encoded by genes HI1470 and HI1471 of Haemophilus influenzae has been solved at 2.4 angstrom resolution. The permeation pathway exhibits an inward-facing conformation, in contrast to the outward-facing state previously observed for the homologous vitamin B12 importer BtuCD. Although the structures of both HI1470/1 and BtuCD have been solved in nucleotide-free states, the pairs of ABC subunits in these two structures differ by a translational shift in the plane of the membrane that coincides with a repositioning of the membrane-spanning subunits. The differences observed between these ABC transporters involve relatively modest rearrangements and may serve as structural models for inward- and outward-facing conformations relevant to the alternating access mechanism of substrate translocation.", "date": "2007-01-19", "date_type": "published", "publication": "Science", "volume": "315", "number": "5810", "publisher": "American Association for the Advancement of Science", "pagerange": "373-377", "id_number": "CaltechAUTHORS:20141112-082347898", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141112-082347898", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "James Irvine Foundation" }, { "agency": "Vallee Foundation" }, { "agency": "Parsons Foundation" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1126/science.1133488", "primary_object": { "basename": "Pinkett-SOM.pdf", "url": "https://authors.library.caltech.edu/records/hsvex-vc439/files/Pinkett-SOM.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Pinkett, H. W.; Lee, A. T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n700t-csw81", "eprint_id": 9607, "eprint_status": "archive", "datestamp": "2023-08-22 07:13:49", "lastmod": "2023-10-16 22:22:57", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "How many metals does it take to fix N2? A mechanistic overview of biological nitrogen fixation", "ispublished": "pub", "full_text_status": "public", "keywords": "IRON-MOLYBDENUM COFACTOR; AZOTOBACTER-VINELANDII NITROGENASE; SELECTIVE FE-57 ENRICHMENT; FERROUS FE4S4 CLUSTER; FEMO-COFACTOR; MOFE-PROTEIN; CENTRAL LIGAND; ACTIVE-SITE; CRYSTALLOGRAPHIC STRUCTURE; CLOSTRIDIUM-PASTEURIANUM", "note": "\u00a9 2006 by the National Academy of Sciences. \n\nEdited by Richard R. Schrock, Massachusetts Institute of Technology, Cambridge, MA, and approved June 28, 2006 (received for review May 19, 2006). Published online on November 6, 2006, 10.1073/pnas.0603978103. \n\nWe thank members of the Howard and Rees groups, past, present, and future, for their contributions to the nitrogenase project in our laboratories. This work was supported in part by National Institutes of Health Grant GM045162.\n\nPublished - HOWpnas06.pdf
", "abstract": "During the process of biological nitrogen fixation, the enzyme nitrogenase catalyzes the ATP-dependent reduction of dinitrogen to ammonia. Nitrogenase consists of two component metalloproteins, the iron (Fe) protein and the molybdenum-iron (MoFe) protein; the Fe protein mediates the coupling of ATP hydrolysis to interprotein electron transfer, whereas the active site of the MoFe protein contains the polynuclear FeMo cofactor, a species composed of seven iron atoms, one molybdenum atom, nine sulfur atoms, an interstitial light atom, and one homocitrate molecule. This Perspective provides an overview of biological nitrogen fixation and introduces three contributions to this special feature that address central aspects of the mechanism and assembly of nitrogenase.", "date": "2006-11-14", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "103", "number": "46", "publisher": "National Academy of Sciences", "pagerange": "17088-17093", "id_number": "CaltechAUTHORS:HOWpnas06", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:HOWpnas06", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1073/pnas.0603978103", "pmcid": "PMC1859894", "primary_object": { "basename": "HOWpnas06.pdf", "url": "https://authors.library.caltech.edu/records/n700t-csw81/files/HOWpnas06.pdf" }, "resource_type": "article", "pub_year": "2006", "author_list": "Howard, James B. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z9pf1-kpd58", "eprint_id": 52781, "eprint_status": "archive", "datestamp": "2023-08-19 16:50:02", "lastmod": "2023-10-18 21:04:58", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Borths-E-L", "name": { "family": "Borths", "given": "Elizabeth L." } }, { "id": "Poolman-B", "name": { "family": "Poolman", "given": "Bert" }, "orcid": "0000-0002-1455-531X" }, { "id": "Hvorup-R-N", "name": { "family": "Hvorup", "given": "Rikki N." } }, { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "In Vitro Functional Characterization of BtuCD-F, the Escherichia coli ABC Transporter for Vitamin B_(12) Uptake", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2005 American Chemical Society\n\nReceived July 8, 2005; Revised Manuscript Received October 4, 2005\n\nWe wish to thank Profs. A. Varshavsky and P. Patterson\nand their groups for the use of their ultracentrifuge and\ngamma counter, respectively, in these studies.\n\nThis research was supported in part by the Swiss National Science\nFoundation, Grant No. 3100A0-103765 (K.P.L.), a Fulbright grant from\nNACEE to support the stay of B.P. in the laboratory of D.C.R., and\nthe Howard Hughes Medical Institute (D.C.R.).", "abstract": "BtuCD is an ATP binding cassette (ABC) transporter that facilitates uptake of vitamin B_(12)\ninto the cytoplasm of Escherichia coli. The crystal structures of BtuCD and its cognate periplasmic binding\nprotein BtuF have been recently determined. We have now explored BtuCD-F function in vitro, both in\nproteoliposomes and in various detergents. BtuCD reconstituted into proteoliposomes has a significant\nbasal ATP hydrolysis rate that is stimulated by addition of BtuF and inhibited by sodium ortho-vanadate.\nWhen using different detergents to solubilize BtuCD, the basal ATP hydrolysis rate, the ability of BtuF\nto stimulate hydrolysis, and the extent to which sodium ortho-vanadate inhibits ATP hydrolysis all vary\nsignificantly. Reconstituted BtuCD can mediate transport of vitamin B_(12) against a concentration gradient\nwhen coupled to ATP hydrolysis by BtuD in the liposome lumen and BtuF outside the liposomes. These\nin vitro studies establish the functional competence of the BtuCD and BtuF preparations used in the\ncrystallographic analyses for both ATPase and transport activities. Furthermore, the tight binding of BtuF\nto BtuCD under the conditions studied suggests that the binding protein may not dissociate from the\ntransporter during the catalytic cycle, which may be relevant to the mechanisms of other ABC transporter\nsystems.", "date": "2005-12-13", "date_type": "published", "publication": "Biochemistry", "volume": "44", "number": "49", "publisher": "American Chemical Society", "pagerange": "16301-16309", "id_number": "CaltechAUTHORS:20141212-144459778", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-144459778", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "3100A0-103765" }, { "agency": "NACEE" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1021/bi0513103", "resource_type": "article", "pub_year": "2005", "author_list": "Borths, Elizabeth L.; Poolman, Bert; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tq7qr-kdf82", "eprint_id": 52057, "eprint_status": "archive", "datestamp": "2023-08-19 16:15:36", "lastmod": "2023-10-18 19:30:57", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tezcan-F-A", "name": { "family": "Tezcan", "given": "F. Akif" }, "orcid": "0000-0002-4733-6500" }, { "id": "Kaiser-J-T", "name": { "family": "Kaiser", "given": "Jens T." }, "orcid": "0000-0002-5948-5212" }, { "id": "Mustafi-D", "name": { "family": "Mustafi", "given": "Debarshi" } }, { "id": "Walton-M-Y", "name": { "family": "Walton", "given": "Mika Y." } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase Complexes: Multiple Docking Sites for a Nucleotide Switch Protein", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2005 American Association for the Advancement of Science.\n\n2 June 2005; Accepted 1 August 2005.\n\nThis work was supported by the NIH and HHMI. F.A.T.\nacknowledges the Helen Hay Whitney Foundation for a postdoctoral fellowship. Operations at Stanford Synchrotron Radiation Laboratory and the Advanced Light Source are funded by the Office of Basic Energy Sciences of the U.S. Department of Energy and NIH. We thank the Parsons and Moore Foundations for support of facilities at Caltech. Coordinates and structure factors for the nf-Av2:Av1, adp-Av2:Av1, and pcp-Av2:Av1 structures have been deposited in the RCSB Protein Data Bank (entries 2AFH, 2AFI, and 2AFK, respectively) for release upon publication.\n\nSupplemental Material - Tezcan.SOM.pdf
", "abstract": "Adenosine triphosphate (ATP) hydrolysis in the nitrogenase complex controls the cycle of association and dissociation between the electron donor adenosine triphosphatase (ATPase) (Fe-protein) and its target catalytic protein (MoFe-protein), driving the reduction of dinitrogen into ammonia. Crystal structures in different nucleotide states have been determined that identify conformational changes in the nitrogenase complex during ATP turnover. These structures reveal distinct and mutually exclusive interaction sites on the MoFe-protein surface that are selectively populated, depending on the Fe-protein nucleotide state. A consequence of these different docking geometries is that the distance between redox cofactors, a critical determinant of the intermolecular electron transfer rate, is coupled to the nucleotide state. More generally, stabilization of distinct docking geometries by different nucleotide states, as seen for nitrogenase, could enable nucleotide hydrolysis to drive the relative motion of protein partners in molecular motors and other systems.", "date": "2005-08-26", "date_type": "published", "publication": "Science", "volume": "309", "number": "5739", "publisher": "American Association for the Advancement of Science", "pagerange": "1377-1380", "id_number": "CaltechAUTHORS:20141121-144257412", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141121-144257412", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Helen Hay Whitney Foundation" }, { "agency": "Department of Energy (DOE)" }, { "agency": "Parsons Foundation" }, { "agency": "Gordon and Betty Moore Foundation" } ] }, "doi": "10.1126/science.1115653", "primary_object": { "basename": "Tezcan.SOM.pdf", "url": "https://authors.library.caltech.edu/records/tq7qr-kdf82/files/Tezcan.SOM.pdf" }, "resource_type": "article", "pub_year": "2005", "author_list": "Tezcan, F. Akif; Kaiser, Jens T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zw33r-75f84", "eprint_id": 86269, "eprint_status": "archive", "datestamp": "2023-08-22 03:31:25", "lastmod": "2023-10-18 19:25:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Tezcan-F-A", "name": { "family": "Tezcan", "given": "F. Akif" }, "orcid": "0000-0002-4733-6500" }, { "id": "Haynes-C-A", "name": { "family": "Haynes", "given": "Chad A." } }, { "id": "Walton-M-Y", "name": { "family": "Walton", "given": "Mika Y." } }, { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana" } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } } ] }, "title": "Structural basis of biological nitrogen fixation", "ispublished": "pub", "full_text_status": "restricted", "keywords": "nitrogenase; iron\u2013sulphur proteins; nucleotide-switch proteins; biological electron transfer", "note": "\u00a9 2005 The Royal Society. \n\nPublished online 5 April 2005. \n\nWe thank the US National Institutes of Health for research support (GM45162) and the Helen Hay Whitney Foundation for a postdoctoral fellowship to F.A.T.", "abstract": "Biological nitrogen fixation is mediated by the nitrogenase enzyme system that catalyses the ATP dependent reduction of atmospheric dinitrogen to ammonia. Nitrogenase consists of two component metalloproteins, the MoFe-protein with the FeMo-cofactor that provides the active site for substrate reduction, and the Fe-protein that couples ATP hydrolysis to electron transfer. An overview of the nitrogenase system is presented that emphasizes the structural organization of the proteins and associated metalloclusters that have the remarkable ability to catalyse nitrogen fixation under ambient conditions. Although the mechanism of ammonia formation by nitrogenase remains enigmatic, mechanistic inferences motivated by recent developments in the areas of nitrogenase biochemistry, spectroscopy, model chemistry and computational studies are discussed within this structural framework.", "date": "2005-04-15", "date_type": "published", "publication": "Philosophical Transactions A: Mathematical, Physical and Engineering Sciences", "volume": "363", "number": "1829", "publisher": "Royal Society of London", "pagerange": "971-984", "id_number": "CaltechAUTHORS:20180507-142707424", "issn": "1364-503X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180507-142707424", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Helen Hay Whitney Foundation" } ] }, "doi": "10.1098/rsta.2004.1539", "resource_type": "article", "pub_year": "2005", "author_list": "Rees, Douglas C.; Tezcan, F. Akif; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/s8j50-ge093", "eprint_id": 1830, "eprint_status": "archive", "datestamp": "2023-08-22 03:00:41", "lastmod": "2023-10-13 23:02:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Cruz-F", "name": { "family": "Cruz", "given": "Francisco" } }, { "id": "Drennan-C-L", "name": { "family": "Drennan", "given": "Catherine L." } }, { "id": "Ramakrishnan-V", "name": { "family": "Ramakrishnan", "given": "Vijay" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Ferry-J-G", "name": { "family": "Ferry", "given": "James G." } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } } ] }, "title": "Structures of the Iron-Sulfur Flavoproteins from Methanosarcina thermophila and Archaeoglobus fulgidus", "ispublished": "pub", "full_text_status": "public", "note": "Copyright \u00a9 2005, American Society for Microbiology \n\nReceived 10 January 2005/ Accepted 21 February 2005 \n\nWe thank Hsiu-Ju Chiu for her assistance with data analysis. \n\nThis work was supported in part by a Marie Curie Intra-European Fellowship within FP6 (to S.L.A.A.), by NIH grants GM45162 (to D.C.R.) and F32-GM19044 (to C.L.D.), and by Department of Energy grant DE-FG02-95ER20198 (to J.G.F.). Stanford Synchrotron Radiation Laboratory operations are funded by the U.S. Department of Energy Office of Basic Energy Sciences and the NIH.", "abstract": "Iron-sulfur flavoproteins (ISF) constitute a widespread family of redox-active proteins in anaerobic prokaryotes. Based on sequence homologies, their overall structure is expected to be similar to that of flavodoxins, but in addition to a flavin mononucleotide cofactor they also contain a cubane-type [4Fe:4S] cluster. In order to gain further insight into the function and properties of ISF, the three-dimensional structures of two ISF homologs, one from the thermophilic methanogen Methanosarcina thermophila and one from the hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus, were determined. The structures indicate that ISF assembles to form a tetramer and that electron transfer between the two types of redox cofactors requires oligomerization to juxtapose the flavin mononucleotide and [4Fe:4S] cluster bound to different subunits. This is only possible between different monomers upon oligomerization. Fundamental differences in the surface properties of the two ISF homologs underscore the diversity encountered within this protein family.", "date": "2005-01-01", "date_type": "published", "publication": "Journal of Bacteriology", "volume": "187", "number": "11", "publisher": "Journal of Bacteriology", "pagerange": "3848-3854", "id_number": "CaltechAUTHORS:ANDjbact05", "issn": "0021-9193", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:ANDjbact05", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1128/JB.187.11.3848-3854.2005", "primary_object": { "basename": "ANDjbact05.pdf", "url": "https://authors.library.caltech.edu/records/s8j50-ge093/files/ANDjbact05.pdf" }, "resource_type": "article", "pub_year": "2005", "author_list": "Andrade, Susana L. A.; Cruz, Francisco; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p64mg-2sv87", "eprint_id": 52780, "eprint_status": "archive", "datestamp": "2023-08-19 15:06:15", "lastmod": "2024-01-13 16:13:11", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Poolman-B", "name": { "family": "Poolman", "given": "Bert" }, "orcid": "0000-0002-1455-531X" }, { "id": "Doeven-M-K", "name": { "family": "Doeven", "given": "Mark K." } }, { "id": "Geertsma-E-R", "name": { "family": "Geertsma", "given": "Eric R." } }, { "id": "Biemans-Oldehinkel-E", "name": { "family": "Biemans-Oldehinkel", "given": "Esther" } }, { "id": "Konings-W-N", "name": { "family": "Konings", "given": "Wil N." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Functional Analysis of Detergent-Solubilized and Membrane-Reconstituted ATP-Binding Cassette Transporters", "ispublished": "unpub", "full_text_status": "restricted", "note": "Copyright 2005, Elsevier Inc. All rights reserved.\n\nThis work was supported by \"Top-subsidie\" Grant 700-50-302 from the Netherlands Organization for Scientific Research-Chemische Wetenschappen, a Fulbright grant from NACEE, and EU-FP6 (E-Mep programme). We thank Nushin Aghajari, Arnold Driessen, Marc LeMaire, and Gea Schuurman-Wolters for sharing information prior to publication.", "abstract": "ATP-binding cassette (ABC) transporters are vital to any living system and are involved in the translocation of a wide variety of substances, from ions and nutrients to high molecular weight proteins. This chapter describes methods used to purify and membrane reconstitute ABC transporters in a fully functional state. The procedures are largely based on our experience with substrate-binding protein-dependent ABC uptake systems from bacteria, but the approaches should be applicable to multisubunit membrane complexes in general. Also, we present simple methods, based on substrate binding or translocation, to follow the activity of the protein complexes in detergent-solubilized and/or membrane-reconstituted state(s).", "date": "2005", "date_type": "published", "publisher": "Academic Press", "place_of_pub": "San Diego, CA", "pagerange": "429-459", "id_number": "CaltechAUTHORS:20141212-144312417", "isbn": "978-0-12-182805-9", "book_title": "Phase II Conjugation Enzymes and Transport Systems", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-144312417", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Netherlands Organization for Scientific Research-Chemische Wetenschappen", "grant_number": "700-50-302" }, { "agency": "NACEE" }, { "agency": "EU-FP6" } ] }, "contributors": { "items": [ { "id": "Sies-H", "name": { "family": "Sies", "given": "Helmut" } }, { "id": "Packer-L", "name": { "family": "Packer", "given": "Lester" } } ] }, "doi": "10.1016/S0076-6879(05)00025-X", "resource_type": "book_section", "pub_year": "2005", "author_list": "Poolman, Bert; Doeven, Mark K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ccrnk-46f90", "eprint_id": 70299, "eprint_status": "archive", "datestamp": "2023-08-22 02:55:35", "lastmod": "2023-10-20 22:07:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Corbett-M-C", "name": { "family": "Corbett", "given": "Mary C." } }, { "id": "Tezcan-F-A", "name": { "family": "Tezcan", "given": "F. Akif" }, "orcid": "0000-0002-4733-6500" }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Walton-M-Y", "name": { "family": "Walton", "given": "Mika Y." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Latimer-M-J", "name": { "family": "Latimer", "given": "Matthew J." } }, { "id": "Hedman-B", "name": { "family": "Hedman", "given": "Britt" } }, { "id": "Hodgson-K-O", "name": { "family": "Hodgson", "given": "Keith O." } } ] }, "title": "Mo K- and L-edge X-ray absorption spectroscopic study of the ADP\u00b7AlF_4^\u2212-stabilized nitrogenase complex: comparison with MoFe protein in solution and single crystal", "ispublished": "pub", "full_text_status": "public", "keywords": "nitrogenase; EXAFS; XAS; diffraction", "note": "\u00a9 2005 International Union of Crystallography. \n\nReceived 23 February 2004; Accepted 22 October 2004. \n\nThis work was supported by NIH grants RR-01209 (KOH) and GM45162 (DCR). The X-ray data were measured at SSRL, a national user facility operated by Stanford University on behalf of the US Department of Energy, Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program and by the DOE, Office of Biological and Environmental Research.\n\nPublished - S0909049504027827.pdf
", "abstract": "The utility of using X-ray absorption spectroscopy (XAS) to study metalloproteins and, specifically, the enzyme complex nitrogenase, is highlighted by this study comparing both the structural and Mo-localized electronic features of the iron-molybdenum cofactor (FeMoco) in isolated MoFe protein and in the ADP\u00b7AlF_4^--stabilized complex of the MoFe protein with the Fe protein. No major differences are found at Mo between the two protein forms. The excellent quality of the data at both the Mo K and L edges will provide a baseline for analysis of other intermediates in the nitrogenase cycle. A new capability to delineate various contributions in the resting state of FeMoco is being pursued through polarized single-crystal XAS. The initial results point to the feasibility of using this technique for the analysis of scattering from the as yet unidentified atom at the center of FeMoco.", "date": "2005", "date_type": "published", "publication": "Journal of Synchrotron Radiation", "volume": "12", "number": "1", "publisher": "Blackwell", "pagerange": "28-34", "id_number": "CaltechAUTHORS:20160913-092647561", "issn": "0909-0495", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160913-092647561", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "RR-01209" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1107/S0909049504027827", "primary_object": { "basename": "S0909049504027827.pdf", "url": "https://authors.library.caltech.edu/records/ccrnk-46f90/files/S0909049504027827.pdf" }, "resource_type": "article", "pub_year": "2005", "author_list": "Corbett, Mary C.; Tezcan, F. Akif; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/66wd8-jfg29", "eprint_id": 52782, "eprint_status": "archive", "datestamp": "2023-08-22 02:36:12", "lastmod": "2023-10-18 21:05:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Becker-C-F-W", "name": { "family": "Becker", "given": "Christian F. W." } }, { "id": "Strop-P", "name": { "family": "Strop", "given": "Pavel" } }, { "id": "Bass-R-B", "name": { "family": "Bass", "given": "Randal B." } }, { "id": "Hansen-K-C", "name": { "family": "Hansen", "given": "Kirk C." } }, { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Ren-Gang", "name": { "family": "Ren", "given": "Gang" } }, { "id": "Yeager-M", "name": { "family": "Yeager", "given": "Mark" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Kochendoerfer-G-G", "name": { "family": "Kochendoerfer", "given": "Gerd G." } } ] }, "title": "Conversion of a Mechanosensitive Channel Protein from a Membrane-Embedded to a Water-Soluble form by Covalent Modification with Amphiphiles", "ispublished": "pub", "full_text_status": "restricted", "keywords": "mechanosensitive channel of large conductance (MscL); water-soluble membrane protein; amphiphiles; light-scattering; electron microscopy", "note": "\u00a9 2004 Elsevier. \n\n(Received 22 July 2004; received in revised form 19 August 2004; accepted 19 August 2004) \n\nWe thank R. Spencer (Merck Research Laboratories) for helpful discussions and for the wild-type Tb_MscL gene used in this study, John Philo (Alliance Protein Laboratories) for dynamic light-scattering studies and analysis, and Chris Garcia (Stanford University) and Stephen Mayo (California Institute of Technology) for helpful discussions and suggestions. This work was supported by NIH PO1 GM062532 (to C.B., P.S., D.R., G.K.) and NIH RO1 HL48908 (to M.Y.). During this work G.R. was supported by a California Universitywide AIDS Research Program Fellowship, and M.Y. was supported, in part, by a Clinical Scientist Award in Translational Research from the Burroughs Wellcome Fund.", "abstract": "Covalent modification of integral membrane proteins with amphiphiles may provide a general approach to the conversion of membrane proteins into water-soluble forms for biophysical and high-resolution structural studies. To test this approach, we mutated four surface residues of the pentameric Mycobacterium tuberculosis mechanosensitive channel of large conductance (MscL) to cysteine residues as anchors for amphiphile attachment. A series of modified ion channels with four amphiphile groups attached per channel subunit was prepared. One construct showed the highest water solubility to a concentration of up to 4 mg/ml in the absence of detergent. This analog also formed native-like, \u03b1-helical homo-pentamers in the absence of detergent as judged by circular dichroism spectroscopy, size-exclusion chromatography and various light-scattering techniques. Proteins with longer, or shorter polymers attached, or proteins modified exclusively with polar cysteine-reactive small molecules, exhibited reduced to no solubility and higher-order aggregation. Electron microscopy revealed a homogeneous population of particles consistent with a pentameric channel. Solubilization of membrane proteins by covalent attachment of amphiphiles results in homogeneous particles that may prove useful for crystallization, solution NMR spectroscopy, and electron microscopy.", "date": "2004-10-22", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "343", "number": "3", "publisher": "Elsevier", "pagerange": "747-758", "id_number": "CaltechAUTHORS:20141212-144652104", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-144652104", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "PO1 GM062532" }, { "agency": "NIH", "grant_number": "RO1 HL48908" }, { "agency": "California Universitywide AIDS Research Program Fellowship" }, { "agency": "Burroughs Wellcome Fund" } ] }, "doi": "10.1016/j.jmb.2004.08.062", "resource_type": "article", "pub_year": "2004", "author_list": "Becker, Christian F. W.; Strop, Pavel; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/bfs3g-tg881", "eprint_id": 52783, "eprint_status": "archive", "datestamp": "2023-08-19 14:19:01", "lastmod": "2023-10-18 21:05:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Nikolic-Hughes-I", "name": { "family": "Nikolic-Hughes", "given": "Ivana" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Herschlag-D", "name": { "family": "Herschlag", "given": "Daniel" } } ] }, "title": "Do Electrostatic Interactions with Positively Charged Active Site Groups Tighten the Transition State for Enzymatic Phosphoryl Transfer?", "ispublished": "pub", "full_text_status": "public", "note": "Copyright \u00a9 2004 American Chemical Society. \n\nReceived April 5, 2004. \n\nWe are grateful to P. Dervan for generously sharing laboratory space and equipment for the aryl sulfate syntheses, A. Heckel and P. Arora for synthetic advice, J. Zalatan for helpful discussions, P. O'Brien and members of the Herschlag and Rees labs for comments on the manuscript. This work was funded by grants from the NIH to D.H. (GM64798) and D.C.R. (GM45162). I.N-H. is an AHA Predoctoral Fellow.\n\nPublished - nikolic-hughes_2004.pdf
", "abstract": "The effect of electrostatic interactions on the transition-state character for enzymatic phosphoryl transfer has been a subject of much debate. In this work, we investigate the transition state for alkaline phosphatase (AP) using linear free-energy relationships (LFERs). We determined kcat/KM for a series of aryl sulfate ester monoanions to obtain the Br\u00f8nsted coefficient, \u03b2lg, and compared the value to that obtained previously for a series of aryl phosphorothioate ester dianion substrates. Despite the difference in substrate charge, the observed Br\u00f8nsted coefficients for AP-catalyzed aryl sulfate and aryl phosphorothioate hydrolysis (\u22120.76 \u00b1 0.14 and \u22120.77 \u00b1 0.10, respectively) are strikingly similar, with steric effects being responsible for the uncertainties in these values. Aryl sulfates and aryl phosphates react via similar loose transition states in solution. These observations suggest an apparent equivalency of the transition states for phosphorothioate and sulfate hydrolysis reactions at the AP active site and, thus, negligible effects of active site electrostatic interactions on charge distribution in the transition state.", "date": "2004-09-29", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "126", "number": "38", "publisher": "American Chemical Society", "pagerange": "11814-11819", "id_number": "CaltechAUTHORS:20141212-144814941", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-144814941", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM64798" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "American Heart Association (AHA) Predoctoral Fellowship" } ] }, "doi": "10.1021/ja0480421", "primary_object": { "basename": "nikolic-hughes_2004.pdf", "url": "https://authors.library.caltech.edu/records/bfs3g-tg881/files/nikolic-hughes_2004.pdf" }, "resource_type": "article", "pub_year": "2004", "author_list": "Nikolic-Hughes, Ivana; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/86dy3-mf123", "eprint_id": 261, "eprint_status": "archive", "datestamp": "2023-08-22 01:22:49", "lastmod": "2023-10-13 20:35:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ambroggio-X-I", "name": { "family": "Ambroggio", "given": "Xavier I." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Deshaies-R-J", "name": { "family": "Deshaies", "given": "Raymond J." }, "orcid": "0000-0002-3671-9354" } ] }, "title": "JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome", "ispublished": "pub", "full_text_status": "public", "keywords": "AfJAMM, A. fulgidus JAMM protein; AMSH, associated molecule with SH3 domain of STAM; CDA, cytidine deaminase; CSN, COP9 signalosome; Cul1, Cullin 1; DUB, deubiquitinating enzyme; JAMM, JAB1/MPN/Mov34 metalloenzyme; MAD, multiwavelength anomalous diffraction; MPN, Mpr1p Pad1p N-terminal\ndomain; Nedd8, neural precursor cell expressed, developmentally downregulated 8; RMS, root-mean squared; Rpn11, regulatory particle number 11; SCF, Skp1/\nCdc53/Cullin/F-box receptor; ScNP, S. caespitosus zinc endoprotease; Ub, ubiquitin; Ubls, ubiquitin-like proteins; UBP, ubiquitin-specific protease; UCH, ubiquitin C-terminal\nhydrolase", "note": "Received August 29, 2003; Accepted October 9, 2003; Published November 24,2003. DOI:10.1371/journal.pbio.0020002.\n\nCopyright: 2003 Ambroggio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the\noriginal work is properly cited.\n\nAcademic Editor: Hidde L. Ploegh, Harvard Medical School\n*To whom correspondence should be addressed. E-mail: deshaies AT caltech.edu\n\nThis work was supported by the National Science Foundation Graduate Research Fellowship and the Gordon Moore Foundation (to XIA), as well as the Howard Hughes Medical Institute (to DCR and RJD). We would like to thank the staff at the Stanford Synchrotron Radiation Laboratory, a national user facility operated by Stanford University on behalf of the United States Department of Energy, Office of Basic Energy Sciences, and the Advanced Light Source, which is supported by the Director of the Office of Science, Office of Basic Energy Sciences, Materials Sciences Division of the United States Department of Energy under contract number DE-AC03-76SF00098 at Lawrence Berkeley National Laboratory. Special thanks go to R. Verma and G. Cope for assistance with the associated biochemistry, T. Yeates and O. Einsle for insights concerning the treatment of the pseudocentered crystals, K. Locher and P. Strop for helpful discussions, and J. Ambroggio for back massages and constant support.\n \nConflicts of interest. The authors have declared that no conflicts of interest exist.\n\nAuthor contributions. XIA, DCR, and RJD conceived and designed the experiments. XIA performed the experiments. XIA, DCR, and RJD analyzed the data. XIA, DCR, and RJD contributed reagents/materials/analysis tools. XIA wrote the paper.\n\nPublished - AMBpb04.pdf
", "abstract": "The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies isopeptidase activities intrinsic to the\nproteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM possesses the key features of a zinc metalloprotease, yet with a distinct fold. The histidine and aspartic acid of the conserved EXnHS/THX7SXXD motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua ligand. By analogy to the active\nsite of thermolysin, we predict that the glutamic acid serves as an acid-base catalyst and the second serine stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these residues are required for Nedd8 isopeptidase activity. The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors.", "date": "2004-01", "date_type": "published", "publication": "PLoS Biology", "volume": "2", "number": "1", "publisher": "Public Library of Science", "pagerange": "113-119", "id_number": "CaltechAUTHORS:AMBpb04", "issn": "1544-9173", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:AMBpb04", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC03-76SF00098" } ] }, "doi": "10.1371/journal.pbio.0020002", "pmcid": "PMC300881", "primary_object": { "basename": "AMBpb04.pdf", "url": "https://authors.library.caltech.edu/records/86dy3-mf123/files/AMBpb04.pdf" }, "resource_type": "article", "pub_year": "2004", "author_list": "Ambroggio, Xavier I.; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/y2ytd-j9g95", "eprint_id": 52784, "eprint_status": "archive", "datestamp": "2023-08-22 01:09:00", "lastmod": "2023-10-18 21:05:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bass-R-B", "name": { "family": "Bass", "given": "Randal B." } }, { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Borths-E-L", "name": { "family": "Borths", "given": "Elizabeth" } }, { "id": "Poon-Y-S", "name": { "family": "Poon", "given": "Yan" } }, { "id": "Strop-P", "name": { "family": "Strop", "given": "Pavel" } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Structures of BtuCD and MscS and their Implications for Transporter and Channel Function", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Transport protein; Mechanosensitive channel; ATP binding cassette transporter; Membrane protein structure", "note": "\u00a9 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.\n\nReceived 25 August 2003; accepted 1 September 2003\n\nResearch in the authors' lab was supported in part by the US National Institutes of Health, grant GM62532, to D.C.R. and a postdoctoral fellowship to R.B.B.", "abstract": "The passage of most molecules across biological membranes is mediated by specialized integral membrane proteins known as channels and transporters. Although these transport families encompass a wide range of functions, molecular architectures and mechanisms, there are common elements that must be incorporated within their structures, namely the translocation pathway, ligand specificity elements and regulatory sensors to control the rate of ligand \u00a3ow across the membrane. This minireview discusses aspects of the structure and mechanism\nof two bacterial transport systems, the stretch-activated mechanosensitive channel of small conductance (MscS) and the ATP-dependent vitamin B12 uptake system (BtuCD), emphasizing their general implications for transporter function.", "date": "2003-11-27", "date_type": "published", "publication": "FEBS Letters", "volume": "555", "number": "1", "publisher": "Elsevier", "pagerange": "111-115", "id_number": "CaltechAUTHORS:20141212-144942986", "issn": "0014-5793", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-144942986", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM62532" } ] }, "doi": "10.1016/S0014-5793(03)01126-8", "resource_type": "article", "pub_year": "2003", "author_list": "Bass, Randal B.; Locher, Kaspar P.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/prxtn-7bf60", "eprint_id": 51889, "eprint_status": "archive", "datestamp": "2023-08-19 11:50:22", "lastmod": "2023-10-18 18:39:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Bass-R-B", "name": { "family": "Bass", "given": "Randal B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Breaching the Barrier", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2003 American Association for the Advancement of Science.\n\nD. C. Rees is an Investigator with the Howard Hughes\nMedical Institute.", "abstract": "Transporter proteins are integral membrane proteins that selectively mediate the passage of molecules across the otherwise impermeable barrier imposed by the phospholipid bilayer that surrounds all cells and organelles. The identification of more than 360 families of transporters\nthrough biochemical and genomic analyses highlights the importance of transport processes to cells. Among the most fascinating transporters are those that act as molecular\npumps, translocating their substrates across membranes against a concentration gradient; this thermodynamically\nunfavorable process is powered by coupling to a second, energetically favorable process such as ATP hydrolysis or the movement of a second solute down a transmembrane\nconcentration gradient.", "date": "2003-08-01", "date_type": "published", "publication": "Science", "volume": "301", "number": "5633", "publisher": "American Association for the Advancement of Science", "pagerange": "603-604", "id_number": "CaltechAUTHORS:20141118-095025111", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141118-095025111", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1126/science.1088621", "resource_type": "article", "pub_year": "2003", "author_list": "Locher, Kaspar P.; Bass, Randal B.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/25sxf-ezr29", "eprint_id": 52785, "eprint_status": "archive", "datestamp": "2023-08-19 11:48:26", "lastmod": "2023-10-18 21:05:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Perozo-E", "name": { "family": "Perozo", "given": "Eduardo" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure and Mechanism in Prokaryotic Mechanosensitive Channels", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2003 Elsevier.", "abstract": "Mechanosensitive channels function as electromechanical switches with the capability to sense the physical state of lipid bilayers. The X-ray crystal structures of MscL and MscS offer a unique opportunity to identify the types of protein motions associated with the opening and closing of these structurally unrelated channels, while providing the framework to address a mechanism of tension sensing that is defined by channel\u2013lipid interactions. Recent functional, structural and dynamic data offer fresh insights into the molecular basis of gating for these membrane proteins.", "date": "2003-08", "date_type": "published", "publication": "Current Opinion in Structural Biology", "volume": "13", "number": "4", "publisher": "Elsevier", "pagerange": "432-442", "id_number": "CaltechAUTHORS:20141212-145107865", "issn": "0959-440X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-145107865", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/S0959-440X(03)00106-4", "resource_type": "article", "pub_year": "2003", "author_list": "Perozo, Eduardo and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/etc4w-07281", "eprint_id": 51683, "eprint_status": "archive", "datestamp": "2023-08-19 11:26:24", "lastmod": "2023-10-18 17:01:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } } ] }, "title": "The Interface Between the Biological and Inorganic Worlds: Iron-Sulfur Metalloclusters", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2003 American Association for the Advancement of Science.\n\nWe thank D. Newman for discussions. This work was\nsupported in part by NIH grant GM45162. Because of\nthe overview nature of this paper, references are not\nexhaustive and primarily serve as entry points to the\nrelevant literature.", "abstract": "Complex iron-sulfur metalloclusters form the active sites of the enzymes that catalyze redox transformations of N_2, CO, and H_2, which are likely components of Earth's primordial atmosphere. Although these centers reflect the organizational principles of simpler iron-sulfur clusters, they exhibit extensive elaborations that confer specific ligand-binding and catalytic properties. These changes were probably achieved through evolutionary processes, including the fusion of small clusters, the addition of new metals, and the development of cluster assembly pathways, driven by selective pressures resulting from changes in the chemical composition of the biosphere.", "date": "2003-05-09", "date_type": "published", "publication": "Science", "volume": "300", "number": "5621", "publisher": "American Association for the Advancement of Science", "pagerange": "929-931", "id_number": "CaltechAUTHORS:20141112-145327502", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141112-145327502", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1126/science.1083075", "resource_type": "article", "pub_year": "2003", "author_list": "Rees, Douglas C. and Howard, James B." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kfn6b-qe408", "eprint_id": 52788, "eprint_status": "archive", "datestamp": "2023-08-19 11:15:26", "lastmod": "2023-10-18 21:35:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shapovalov-G", "name": { "family": "Shapovalov", "given": "George" } }, { "id": "Bass-R-B", "name": { "family": "Bass", "given": "Randal" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lester-H-A", "name": { "family": "Lester", "given": "Henry A." }, "orcid": "0000-0002-5470-5255" } ] }, "title": "Open-State Disulfide Crosslinking between Mycobacterium tuberculosis Mechanosensitive Channel Subunits", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2003 by the Biophysical Society. \n\nSubmitted August 30, 2002, and accepted for publication December 9,\n2002. \n\nWe thank Sergei Sukharev and Paul Blount for introducing us to MscL electrophysiology, Josh Maurer for mutants and cells, and Ido Braslavsky, Donald Elmore, Steve Quake, Gerd Kochendoerfer, and Dennis Dougherty for valuable discussion.\n\nThis research was supported by a grant from the National Institutes of Health (GM-062532), by a Burroughs-Wellcome Fund Computation and Molecular Biology Fellowship to George Shapovalov, and by an National Research Service Award to Randal Bass (GM-020705).\n\nPublished - shapovalov_2003.pdf
", "abstract": "The mechanosensitive channel of large conductance from Mycobacterium tuberculosis (Tb-MscL) was subjected to cysteine-scanning mutagenesis at several residues in the M1 region. The V15C channel displayed disulfide crosslinking in air, but not in the presence of 100 mM \u03b2-mercaptoethanol. In single-channel experiments, the V15C channel was more sensitive to tension than was wild-type Tb-MscL. In air, Tb-MscL V15C occasionally displayed signature-events: at constant tension, there was first a sojourn in the highest conductance open state, then a series of transitions to substates. During a signature-event, these transitions do not appear to be reversible. Some sojourns in the lower conductance states lasted for \u2265100 s. These signature-events were abolished by 100 mM \u03b2-mercaptoethanol and did not occur in a cysteineless gain-of-function mutant, suggesting that the signature-events represent disulfide crosslinking between channel subunits. We conclude that the crosslinking occurs during an open state during asymmetric sojourns that bring the \u03b1-carbons of adjacent 15C side chains within 3.6\u20136.8 \u00c5. Such asymmetric structures must be considered in models of TB-MscL gating.", "date": "2003-04", "date_type": "published", "publication": "Biophysical Journal", "volume": "84", "number": "4", "publisher": "Biophysical Society", "pagerange": "2357-2365", "id_number": "CaltechAUTHORS:20141212-145345633", "issn": "0006-3495", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-145345633", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-062532" }, { "agency": "Burroughs-Wellcome Fund" }, { "agency": "NIH", "grant_number": "GM-020705" } ] }, "doi": "10.1016/S0006-3495(03)75041-3", "pmcid": "PMC1302802", "primary_object": { "basename": "shapovalov_2003.pdf", "url": "https://authors.library.caltech.edu/records/kfn6b-qe408/files/shapovalov_2003.pdf" }, "resource_type": "article", "pub_year": "2003", "author_list": "Shapovalov, George; Bass, Randal; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r4st3-vh249", "eprint_id": 52789, "eprint_status": "archive", "datestamp": "2023-08-19 10:33:34", "lastmod": "2024-01-13 16:13:13", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Strop-Pavel", "name": { "family": "Strop", "given": "Pavel" } }, { "id": "Bass-Randal-B", "name": { "family": "Bass", "given": "Randal" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Prokaryotic Mechanosensitive Channels", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2003 Elsevier. \n\nDiscussions with Sidney Wang, Meg Barclay, Rober Spencer, Kaspar Locher, Geoffrey Chang, Dennis Dougherty, Henry Lester, Rob Phillips, and Eduardo Perozo are greatly appreciated. This work was supported in part by NIH grants GM62532 to D.C.R. and GM20705 to R.B.B.", "abstract": "Mechanosensitive ion channels are integral membrane proteins that open and close in response to mechanical stress applied either directly to the cell membrane (in the case of intrinsically mechanosensitive channels) or indirectly, through forces applied to other cytoskeletal components. Cellular phenomena mediated by mechanosensitive channels include touch, hearing, cardiovascular tone, detection of gravity, pressure sensation, pain perception, and osmoregulation. Mechanosensirive channels are quite diverse both physiologically and structurally and have been discovered in all fundamental branches of the phylogenetic tree, Eubacteria, Eukarya, and Archaea. Eukaryotic mechanosensitive channels include the TRPV subclass of the Transient Receptor Potential channel family: the TREK-1 and TRAAK members of the two-pore domain potassium channel family K2p; and the DEG/ENaC superfamily composed of degenerins, eptithelial sodium channels, and acid-sensing channels that have been implicated in the touch response of nematodes. Although many of these channels, including the degenerins and the yet-to-be identified channel receptors involved in hearing, appear to have an obligatory requirement for cytoskeletal coupling, others, such as the TREK-1 and TRAAK channels, exhibit intrisinic mechanosensitive activity.", "date": "2003", "date_type": "published", "publisher": "Elsevier", "place_of_pub": "New York, NY", "pagerange": "177-209", "id_number": "CaltechAUTHORS:20141212-145528968", "isbn": "978-0-12-034263-1", "book_title": "Membrane Proteins", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-145528968", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM62532" }, { "agency": "NIH", "grant_number": "GM20705" } ] }, "contributors": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "doi": "10.1016/S0065-3233(03)63008-1", "resource_type": "book_section", "pub_year": "2003", "author_list": "Strop, Pavel; Bass, Randal; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kzk8p-6tf54", "eprint_id": 52790, "eprint_status": "archive", "datestamp": "2023-08-19 10:29:19", "lastmod": "2023-10-18 21:35:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schmid-B", "name": { "family": "Schmid", "given": "Benedikt" } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Chiu-H-J", "name": { "family": "Chiu", "given": "Hsui-Ju" } }, { "id": "Willing-A", "name": { "family": "Willing", "given": "Andreas" } }, { "id": "Yoshida-M", "name": { "family": "Yoshida", "given": "Mika" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Biochemical and Structural Characterization of the Cross-linked Complex of Nitrogenase: Comparison to the ADP-AIF_4^--Stabilized Structure", "ispublished": "pub", "full_text_status": "restricted", "note": "Copyright \u00a9 2002 American Chemical Society. \n\nReceived August 15, 2002. Revised Manuscript Received October 27, 2002. \n\nWe thank A. Deacon and the staff at the Stanford Synchrotron Radiation Laboratory for assistance with data collection.", "abstract": "The transient formation of a complex between the component Fe- and MoFe-proteins of nitrogenase represents a central event in the substrate reduction mechanism of this enzyme. Previously, we have isolated an N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide (EDC) cross-linked complex of these proteins stabilized by a covalent isopeptide linkage between Glu 112 and Lys \u03b2400 of the Fe-protein and MoFe-protein, respectively [Willing, A., et al. (1989) J. Biol. Chem. 264, 8499\u22128503; Willing, A., and Howard, J. B. (1990) J. Biol. Chem. 265, 6596\u22126599]. We report here the biochemical and structural characterization of the cross-linked complex to assess the mechanistic relevance of this species. Glycinamide inhibits the cross-linking reaction, and is found to be specifically incorporated into Glu 112 of the Fe-protein, without detectable modification of either of the neighboring residues (Glu 110 and Glu 111). This modified protein is still competent for substrate reduction, demonstrating that formation of the cross-linked complex is responsible for the enzymatic inactivation, and not the EDC reaction or the modification of the Fe-protein. Crystallographic analysis of the EDC-cross-linked complex at 3.2 \u00c5 resolution confirms the site of the isopeptide linkage. The nature of the protein surfaces around the cross-linking site suggests there is a strong electrostatic component to the formation of the complex, although the interface area between the component proteins is small. The binding footprints between proteins in the cross-linked complex are adjacent, but with little overlap, to those observed in the complex of the nitrogenase proteins stabilized by ADP-AlF_4^-. The results of these studies suggest that EDC cross-linking traps a nucleotide-independent precomplex of the nitrogenase proteins driven by complementary electrostatic interactions that subsequently rearranges in a nucleotide-dependent fashion to the electron transfer competent state observed in the ADP-AlF_4^- structure.", "date": "2002-12-31", "date_type": "published", "publication": "Biochemistry", "volume": "41", "number": "52", "publisher": "American Chemical Society", "pagerange": "15557-15565", "id_number": "CaltechAUTHORS:20141212-145725733", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141212-145725733", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1021/bi026642b", "resource_type": "article", "pub_year": "2002", "author_list": "Schmid, Benedikt; Einsle, Oliver; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1p6bt-5fh95", "eprint_id": 679, "eprint_status": "archive", "datestamp": "2023-08-21 23:58:22", "lastmod": "2023-10-13 21:55:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Borths-E-L", "name": { "family": "Borths", "given": "Elizabeth L." } }, { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The structure of Escherichia coli BtuF and binding to its cognate ATP binding cassette transporter", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2002 by The National Academy of Sciences. \n\nContributed by Douglas C. Rees and approved October 30, 2002. \n\nPublished online before print December 10, 2002, 10.1073/pnas.262659699 \n\nData deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID code 1N2Z).\n\nPublished - BORpnas02.pdf
", "abstract": "Bacterial binding protein-dependent ATP binding cassette (ABC) transporters facilitate uptake of essential nutrients. The crystal structure of Escherichia coli BtuF, the protein that binds vitamin B12 and delivers it to the periplasmic surface of the ABC transporter BtuCD, reveals a bi-lobed fold resembling that of the ferrichrome binding protein FhuD. B12 is bound in the \"base-on\" conformation in a deep cleft formed at the interface between the two lobes of BtuF. A stable complex between BtuF and BtuCD (with the stoichiometry BtuC2D2F) is demonstrated to form in vitro and was modeled using the individual crystal structures. Two surface glutamates from BtuF may interact with arginine residues on the periplasmic surface of the BtuCD transporter. These glutamate and arginine residues are conserved among binding proteins and ABC transporters mediating iron and B12 uptake, suggesting that they may have a role in docking and the transmission of conformational changes.", "date": "2002-12-24", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "99", "number": "26", "publisher": "National Academy of Sciences", "pagerange": "16642-16647", "id_number": "CaltechAUTHORS:BORpnas02", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:BORpnas02", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1073/pnas.262659699", "pmcid": "PMC139197", "primary_object": { "basename": "BORpnas02.pdf", "url": "https://authors.library.caltech.edu/records/1p6bt-5fh95/files/BORpnas02.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Borths, Elizabeth L.; Locher, Kaspar P.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/c7dj7-9yw70", "eprint_id": 51677, "eprint_status": "archive", "datestamp": "2023-08-19 10:19:22", "lastmod": "2023-10-18 17:01:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bass-Randal-B", "name": { "family": "Bass", "given": "Randal B." } }, { "id": "Strop-Pavel", "name": { "family": "Strop", "given": "Pavel" } }, { "id": "Barclay-Margaret-T", "name": { "family": "Barclay", "given": "Margaret" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structure of Escherichia coli MscS, a Voltage-Modulated and Mechanosensitive Channel", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2002 American Association for the Advancement of Science.\n\nReceived 30 August 2002; accepted 7 October 2002.\n\nSupported by NIH (D.C.R.) and by a National Service\nResearch Award postdoctoral fellowship\n(R.B.B.). Discussions with R. Spencer, K. Locher, A.\nLee, O. Einsle, D. Dougherty, and H. Lester are\ngreatly appreciated. We thank the staffs at the\nAdvanced Light Source, Advanced Photon Source,\nNational Synchrotron Light Source, and the Stanford\nSynchrotron Radiation Laboratory (SSRL) facilities\nfor their invaluable assistance. These facilities\nare funded by the Office of Basic Energy\nSciences, U.S. Department of Energy, and NIH. The\ncoordinates have been deposited in the Protein\nData Bank (1MXM) for release upon publication.\n\nSupplemental Material - BassSOM.pdf
", "abstract": "The mechanosensitive channel of small conductance (MscS) responds both to stretching of the cell membrane and to membrane depolarization. The crystal structure at 3.9 angstroms resolution demonstrates thatEscherichia coli MscS folds as a membrane-spanning heptamer with a large cytoplasmic region. Each subunit contains three transmembrane helices (TM1, -2, and -3), with the TM3 helices lining the pore, while TM1 and TM2, with membrane-embedded arginines, are likely candidates for the tension and voltage sensors. The transmembrane pore, apparently captured in an open state, connects to a large chamber, formed within the cytoplasmic region, that connects to the cytoplasm through openings that may function as molecular filters. Although MscS is likely to be structurally distinct from other ion channels, similarities in gating mechanisms suggest common structural elements.", "date": "2002-11-22", "date_type": "published", "publication": "Science", "volume": "298", "number": "5598", "publisher": "American Association for the Advancement of Science", "pagerange": "1582-1587", "id_number": "CaltechAUTHORS:20141112-142214604", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141112-142214604", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "National Service Research Award" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1126/science.1077945", "primary_object": { "basename": "BassSOM.pdf", "url": "https://authors.library.caltech.edu/records/c7dj7-9yw70/files/BassSOM.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Bass, Randal B.; Strop, Pavel; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0ypz0-ka812", "eprint_id": 5472, "eprint_status": "archive", "datestamp": "2023-08-21 23:41:43", "lastmod": "2023-10-16 19:14:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeh-A-P", "name": { "family": "Yeh", "given": "Andrew P." } }, { "id": "Ambroggio-X-I", "name": { "family": "Ambroggio", "given": "Xavier I." } }, { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Chatelet-C", "name": { "family": "Chatelet", "given": "Claire" } }, { "id": "Meyer-J", "name": { "family": "Meyer", "given": "Jacques" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "High Resolution Crystal Structures of the Wild Type and Cys-55 right-arrow Ser and Cys-59 right-arrow Ser Variants of the Thioredoxin-like [2Fe-2S] Ferredoxin from Aquifex aeolicus", "ispublished": "pub", "full_text_status": "public", "note": "Copyright \u00a9 2002 by The American Society for Biochemistry and Molecular Biology, Inc. \n\nReceived for publication, May 23, 2002, and in revised form, June 25, 2002. Originally published In Press as doi:10.1074/jbc.M205096200 on June 27, 2002 \n\nPortions of this research were carried out at the Stanford Synchrotron Radiation Laboratory, a national user facility operated by Stanford University on behalf of the United States Department of Energy, Office of Basic Energy Sciences. The Stanford Synchrotron Radiation Laboratory Structural Molecular Biology Program is supported by the Department of Energy and the National Institutes of Health. \n\nThis work was supported by National Institutes of Health Grant GM45062 (to D.C.R.) and by a predoctoral fellowship from the National Science Foundation (to X.I.A.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. \n\nThe atomic coordinates and the structure factors (code 1M2A, 1M2B and 1M2D) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).", "abstract": "The [2Fe-2S] ferredoxin (Fd4) from Aquifex aeolicus adopts a thioredoxin-like polypeptide fold that is distinct from other [2Fe-2S] ferredoxins. Crystal structures of the Cys-55 right-arrow Ser (C55S) and Cys-59 right-arrow Ser (C59S) variants of this protein have been determined to 1.25 \u00c5 and 1.05 \u00c5 resolution, respectively, whereas the resolution of the wild type (WT) has been extended to 1.5 \u00c5. The improved WT structure provides a detailed description of the [2Fe-2S] cluster, including two features that have not been noted previously in any [2Fe-2S] cluster-containing protein, namely, pronounced distortions in the cysteine coordination to the cluster and a Calpha -H-Sgamma hydrogen bond between cluster ligands Cys-55 and Cys-9. These features may contribute to the unusual electronic and magnetic properties of the [2Fe-2S] clusters in WT and variants of this ferredoxin. The structures of the two variants of Fd4, in which single cysteine ligands to the [2Fe-2S] cluster are replaced by serine, establish the metric details of serine-ligated Fe-S active sites with unprecedented accuracy. Both the cluster and its surrounding protein matrix change in subtle ways to accommodate this ligand substitution, particularly in terms of distortions of the Fe2S2 inorganic core from planarity and displacements of the polypeptide chain. These high resolution structures illustrate how the interactions between polypeptide chains and Fe-S active sites reflect combinations of flexibility and rigidity on the part of both partners; these themes are also evident in more complex systems, as exemplified by changes associated with serine ligation of the nitrogenase P cluster.", "date": "2002-09-13", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "277", "number": "37", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "34499-34507", "id_number": "CaltechAUTHORS:YEHjbc02", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:YEHjbc02", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1074/jbc.M205096200", "primary_object": { "basename": "YEHjbc02.pdf", "url": "https://authors.library.caltech.edu/records/0ypz0-ka812/files/YEHjbc02.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Yeh, Andrew P.; Ambroggio, Xavier I.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1k9bq-kcw78", "eprint_id": 51803, "eprint_status": "archive", "datestamp": "2023-08-19 10:02:17", "lastmod": "2023-10-18 17:10:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Tezcan-F-A", "name": { "family": "Tezcan", "given": "F. Akif" }, "orcid": "0000-0002-4733-6500" }, { "id": "Andrade-S-L-A", "name": { "family": "Andrade", "given": "Susana L. A." } }, { "id": "Schmid-B", "name": { "family": "Schmid", "given": "Benedikt" } }, { "id": "Yoshida-Mika", "name": { "family": "Yoshida", "given": "Mika" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase MoFe-Protein at 1.16 \u00c5 Resolution: A Central Ligand in the FeMo-Cofactor", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2002 American Association for the Advancement of Science.\n\n13 May 2002; Accepted 26 June 2002.\n\nThis work was supported by NIH. Stanford Synchrotron\nRadiation Laboratory operations are funded by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences, and NIH. F.A.T. acknowledges the Burroughs Wellcome Fund and the Helen Hay Whitney Foundation for postdoctoral fellowships. We thank J. C. Peters, J. E. Bercaw, and H. B. Gray for enlightening discussions. Coordinates of the refined MoFe-protein structure have been deposited in the Protein Data Bank (accession code 1M1N).\n\nSupplemental Material - Einsle1073877.sup.pdf
", "abstract": "A high-resolution crystallographic analysis of the nitrogenase MoFe-protein reveals a previously unrecognized ligand coordinated to six iron atoms in the center of the catalytically essential FeMo-cofactor. The electron density for this ligand is masked in structures with resolutions lower than 1.55 angstroms, owing to Fourier series termination ripples from the surrounding iron and sulfur atoms in the cofactor. The central atom completes an approximate tetrahedral coordination for the six iron atoms, instead of the trigonal coordination proposed on the basis of lower resolution structures. The crystallographic refinement at 1.16 angstrom resolution is consistent with this newly detected component being a light element, most plausibly nitrogen. The presence of a nitrogen atom in the cofactor would have important implications for the mechanism of dinitrogen reduction by nitrogenase.", "date": "2002-09-06", "date_type": "published", "publication": "Science", "volume": "297", "number": "5587", "publisher": "American Association for the Advancement of Science", "pagerange": "1696-1700", "id_number": "CaltechAUTHORS:20141114-150119485", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141114-150119485", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Department of Energy (DOE)" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Helen Hay Whitney Foundation" } ] }, "doi": "10.1126/science.1073877", "primary_object": { "basename": "Einsle1073877.sup.pdf", "url": "https://authors.library.caltech.edu/records/1k9bq-kcw78/files/Einsle1073877.sup.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Einsle, Oliver; Tezcan, F. Akif; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n9eg8-6cj84", "eprint_id": 72588, "eprint_status": "archive", "datestamp": "2023-08-19 09:54:29", "lastmod": "2024-01-13 20:21:44", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Metalloproteins to Membrane Proteins: Biological Energy Transduction Mechanisms", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2002 American Chemical Society. \n\nPublished in print 7 August 2002.\n\nI would like to thank the Colonel for his advice and guidance over the years, as well as allowing us to collect the first data sets of the nitrogenase Fe-protein in his lab. None of this work would have been possible without my interactions with Jim Howard, or without the efforts of my group on the projects described from my lab. Research work on nitrogenase and MscL has been supported by NIH grants GM45162 and GM62532, respectively.", "abstract": "Structural analyses of two macromolecular systems, the metalloprotein nitrogenase and the integral membrane protein MscL (mechanosensitive channel of large conductance), are discussed within the context of energy transduction mechanisms. Nitrogenase catalyzes the ATP dependent reduction of dinitrogen to ammonia during the process of biological nitrogen fixation, while MscL is a stretch activated (mechanosensitive) channel that opens and closes in response to changes in lateral tension applied to membranes. Although nitrogenase and MscL have very different structures and functions, they both mediate the coupling of two energetic processes. From these studies, it is suggested that effective coupling of two processes by transduction proteins occurs through conformational states common to each process.", "date": "2002-08-07", "date_type": "published", "publisher": "American Chemical Society", "place_of_pub": "Washington, DC", "pagerange": "202-215", "id_number": "CaltechAUTHORS:20161206-084656751", "isbn": "9780841237360", "book_title": "Structures and Mechanisms", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161206-084656751", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "GM62532" } ] }, "doi": "10.1021/bk-2002-0827.ch013", "resource_type": "book_section", "pub_year": "2002", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/s384j-w8g05", "eprint_id": 7659, "eprint_status": "archive", "datestamp": "2023-08-21 23:28:33", "lastmod": "2023-10-16 21:01:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Great metalloclusters in enzymology", "ispublished": "pub", "full_text_status": "public", "keywords": "metalloproteins, iron-sulfur clusters, nitrogenase, hydrogenase, carbon monoxide dehydrogenase, nitrous oxide reductase", "note": "\"Reprinted, with permission, from the Annual Review of Biochemistry, Volume 71 copyright 2002 by Annual Reviews, www.annualreviews.org\" \n\nDiscussions with James B. Howard, Benedikt Schmid, Jessica Chiu, Pavel Strop, Oliver Einsle, and Akif Tezcan are, as always, greatly appreciated. Research in the author's laboratory was supported in part by U.S. Public Health Service grant GM45162.\n\nPublished - REEarb02.pdf
", "abstract": "Metallocluster-containing enzymes catalyze some of the most basic redox transformations in the biosphere. The reactions catalyzed by these enzymes typically involve small molecules such as N2, CO, and H2 that are used to generate both chemical building blocks and energy for metabolic purposes. During the past decade, structures have been established for the iron-sulfur-based metalloclusters present in the molybdenum nitrogenase, the iron-only hydrogenase, and the nickel-carbon monoxide dehydrogenase, and for the copper-sulfide-based cluster in nitrous oxide reductase. Although these clusters are built from interactions observed in simpler metalloproteins, they contain novel features that may be relevant for their catalytic function. The mechanisms of metallocluster-containing enzymes are still poorly defined, and represent substantial and continuing challenges to biochemists, biophysicists, and synthetic chemists. These proteins also provide a window into the union of the biological and inorganic worlds that may have been relevant to the early evolution of biochemical catalysis.", "date": "2002-07", "date_type": "published", "publication": "Annual Review of Biochemistry", "volume": "71", "publisher": "Annual Reviews", "pagerange": "221-246", "id_number": "CaltechAUTHORS:REEarb02", "issn": "0066-4154", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:REEarb02", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1146/annurev.biochem.71.110601.135406", "primary_object": { "basename": "REEarb02.pdf", "url": "https://authors.library.caltech.edu/records/s384j-w8g05/files/REEarb02.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zbkhv-bv028", "eprint_id": 1567, "eprint_status": "archive", "datestamp": "2023-08-21 23:21:14", "lastmod": "2023-10-13 22:52:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Spencer-R-H", "name": { "family": "Spencer", "given": "Robert H." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "\u00adDouglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The alpha-helix and the organization and gating of channels", "ispublished": "pub", "full_text_status": "public", "keywords": "ION CHANNELS; MEMBRANE PROTEINS; TRANSMEMBRANE HELICES; CONFORMATIONAL CHANGES; MECHANOSENSITIVE ION-CHANNEL; PHOTOSYNTHETIC REACTION-CENTER; CYTOCHROME-C-OXIDASE; GATED K+ CHANNEL; SHAKER POTASSIUM CHANNEL; PROTEIN-DATA-BANK; MEMBRANE-PROTEINS; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE", "note": "\"Reprinted, with permission, from the Annual Review of Biophysics and Biomolecular Structure, Volume 31 copyright 2002 by Annual Reviews, www.annualreviews.org\" \n\nDiscussions with Randal Bass, Kaspar Locher, Pavel Strop, Allen Lee, Margaret Barclay, Dennis Dougherty, Henry Lester, and Chris Miller are greatly appreciated. This work was supported in part by NIH grant GM62532.", "abstract": "The structures of an increasing number of channels and other a-helical membrane proteins have been determined recently, including the KcsA potassium channel, the MscL mechanosensitive channel, and the AQP1 and GlpF members of the aquaporin family. In this chapter, the orientation and packing characteristics of bilayer-spanning helices are surveyed in integral membrane proteins. In the case of channels, a-helices create the scaled barrier that separates the hydrocarbon region of the bilayer from the permeation pathway for solutes. The helices surrounding the permeation pathway tend to be rather steeply tilted relative to the membrane normal and are consistently arranged in a right-handed bundle. The helical framework further provides a supporting scaffold for nonmembrane-spanning structures associated with channel selectivity. Although structural details remain scarce, the conformational changes associated with gating transitions between closed and open states of channels are reviewed, emphasizing the potential roles of helix-helix interactions in this process.", "date": "2002-06", "date_type": "published", "publication": "Annual Review of Biophysics and Biomolecular Structure", "volume": "31", "publisher": "Annual Reviews", "pagerange": "207-233", "id_number": "CaltechAUTHORS:SPEarbbs02", "issn": "1056-8700", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:SPEarbbs02", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1146/annurev.biophys.31.082901.134329", "primary_object": { "basename": "SPEarbbs02.pdf", "url": "https://authors.library.caltech.edu/records/zbkhv-bv028/files/SPEarbbs02.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Spencer, Robert H. and Rees, \u00adDouglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wmheh-xkm18", "eprint_id": 53399, "eprint_status": "archive", "datestamp": "2023-08-21 23:20:58", "lastmod": "2023-10-19 14:50:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Axelrod-H-L", "name": { "family": "Axelrod", "given": "Herbert L." } }, { "id": "Abresch-E-C", "name": { "family": "Abresch", "given": "Edward C." } }, { "id": "Okamura-M-Y", "name": { "family": "Okamura", "given": "Melvin Y." } }, { "id": "Yeh-A-P", "name": { "family": "Yeh", "given": "Andrew P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Feher-G", "name": { "family": "Feher", "given": "George" } } ] }, "title": "X-ray Structure Determination of the Cytochrome c_2: Reaction Center Electron Transfer Complex from Rhodobacter sphaeroides", "ispublished": "pub", "full_text_status": "restricted", "keywords": "bacterial photosynthesis; protein-protein interaction; electron transfer proteins; membrane proteins; protein complexes", "note": "\u00a9 2002 Elsevier Science Ltd.\n\nReceived 28 November 2001; received in revised form 18 February 2002; accepted 25 February 2002.\n\nWe thank R. Isaacson for his expert help in designing and running the microspectrophotometer, Keith Henderson at the Advanced Light Source (ALS), and the staff at the Stanford Synchrotron Radiation Laboratory (SSRL) for their advice and assistance with the X-ray data collections; Mark Paddock, Raphael Calvo, Les Dutton, Marilyn Gunner, and Jose Onuchic for helpful discussions. The synchrotron X-ray data collection facilities are supported by the U.S. Department of Energy (ALS, SSRL) and NIH (SSRL). This work was supported by the National Institutes of Health (grant number GM-13191 to G. F. and GM-45162 to D. C. R.) and National Science Foundation (grant number\n9974568 to M.Y.O.).", "abstract": "In the photosynthetic bacterium Rhodobacter sphaeroides, a water soluble cytochrome c_2 (cyt c_2) is the electron donor to the reaction center (RC), the membrane-bound pigment\u2013protein complex that is the site of the primary light-induced electron transfer. To determine the interactions important for docking and electron transfer within the transiently bound complex of the two proteins, RC and cyt c_2 were co-crystallized in two monoclinic crystal forms. Cyt c_2 reduces the photo-oxidized RC donor (D+), a bacteriochlorophyll dimer, in the co-crystals in \u223c0.9 \u03bcs, which is the same time as measured in solution. This provides strong evidence that the structure of the complex in the region of electron transfer is the same in the crystal and in solution. X-ray diffraction data were collected from co-crystals to a maximum resolution of 2.40 \u00c5 and refined to an R-factor of 22% (R_(free)=26%). The structure shows the cyt c_2 to be positioned at the center of the periplasmic surface of the RC, with the heme edge located above the bacteriochlorophyll dimer. The distance between the closest atoms of the two cofactors is 8.4 \u00c5. The side-chain of Tyr L162 makes van der Waals contacts with both cofactors along the shortest intermolecular electron transfer pathway. The binding interface can be divided into two domains: (i) A short-range interaction domain that includes Tyr L162, and groups exhibiting non-polar interactions, hydrogen bonding, and a cation\u2013\u03c0 interaction. This domain contributes to the strength and specificity of cyt c_2 binding. (ii) A long-range, electrostatic interaction domain that contains solvated complementary charges on the RC and cyt c_2. This domain, in addition to contributing to the binding, may help steer the unbound proteins toward the right conformation.", "date": "2002-05-31", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "319", "number": "2", "publisher": "Elsevier", "pagerange": "501-515", "id_number": "CaltechAUTHORS:20150108-152754099", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-152754099", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "GM-13191" }, { "agency": "NIH", "grant_number": "GM-45162" }, { "agency": "NSF", "grant_number": "9974568" } ] }, "doi": "10.1016/S0022-2836(02)00168-7", "resource_type": "article", "pub_year": "2002", "author_list": "Axelrod, Herbert L.; Abresch, Edward C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sf8p2-nnt07", "eprint_id": 51806, "eprint_status": "archive", "datestamp": "2023-08-19 09:29:46", "lastmod": "2023-10-18 17:11:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The E. coli BtuCD Structure: A Framework for ABC Transporter Architecture and Mechanism", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2002 American Association for the Advancement of Science.\n\nReceived 21 February 2002; accepted 21 March 2002.\n\nWe thank the staff at the Stanford Synchrotron Radiation\nLaboratory (SSRL), the Advanced Photon Source\n(APS), the Advanced Light Source (ALS), and the National\nSynchrotron Light Source (NSLS) for their support\nduring crystal screening and data collection. We also\nthank M. Barclay, R. Bass, O. Einsle, I. Locher-Hinderling,\nand P. Strop for helpful discussions. We further thank M.\nDay for assistance in obtaining the cyclotetravanadate\ncoordinates, and L. Ackerman and J. Bercaw for their\nhelp in the synthesis of inorganic clusters during the\nsearch for derivatives. The coordinates of the BtuCD\ntransporter with bound cyclotetravanadate have been\ndeposited in the Protein Data Bank (www.rcsb.org/pdb)\nwith access code IL7V.\n\nSupplemental Material - suppdata.pdf
", "abstract": "The ABC transporters are ubiquitous membrane proteins that couple adenosine triphosphate (ATP) hydrolysis to the translocation of diverse substrates across cell membranes. Clinically relevant examples are associated with cystic fibrosis and with multidrug resistance of pathogenic bacteria and cancer cells. Here, we report the crystal structure at 3.2 angstrom resolution of the Escherichia coli BtuCD protein, an ABC transporter mediating vitamin B_(12) uptake. The two ATP-binding cassettes (BtuD) are in close contact with each other, as are the two membrane-spanning subunits (BtuC); this arrangement is distinct from that observed for the E. coli lipid flippase MsbA. The BtuC subunits provide 20 transmembrane helices grouped around a translocation pathway that is closed to the cytoplasm by a gate region whereas the dimer arrangement of the BtuD subunits resembles the ATP-bound form of the Rad50 DNA repair enzyme. A prominent cytoplasmic loop of BtuC forms the contact region with the ATP-binding cassette and appears to represent a conserved motif among the ABC transporters.", "date": "2002-05-10", "date_type": "published", "publication": "Science", "volume": "296", "number": "5570", "publisher": "American Association for the Advancement of Science", "pagerange": "1091-1098", "id_number": "CaltechAUTHORS:20141114-153101236", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141114-153101236", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1126/science.1071142", "primary_object": { "basename": "suppdata.pdf", "url": "https://authors.library.caltech.edu/records/sf8p2-nnt07/files/suppdata.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Locher, Kaspar P.; Lee, Allen T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5mcyw-r5876", "eprint_id": 4846, "eprint_status": "archive", "datestamp": "2023-08-21 23:18:37", "lastmod": "2023-10-16 17:58:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Luna-Chavez-C", "name": { "family": "Luna-Chavez", "given": "C\u00e9sar" } }, { "id": "Croal-L-R", "name": { "family": "Croal", "given": "Laura R." } }, { "id": "Cecchini-G", "name": { "family": "Cecchini", "given": "Gary" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site", "ispublished": "pub", "full_text_status": "public", "keywords": "CYTOCHROME BC(1) COMPLEX; SUCCINATE-UBIQUINONE OXIDOREDUCTASE; ANCHORING SUBUNIT QPS3; WOLINELLA-SUCCINOGENES; PROTON-TRANSFER; RESPIRATORY COMPLEX; ELECTRON-TRANSPORT; HEART-MITOCHONDRIA; CATALYTIC ACTIVITY; DEHYDROGENASE", "note": "Copyright \u00a9 2002 by the American Society for Biochemistry and Molecular Biology. \n\nReceived for publication, January 25, 2002, and in revised form, February 15, 2002. \n\nWe thank A. P. Yeh, R. B. Bass, and A. Dunn for experimental assistance, H. Miyoshi for generously providing the DNP-19 inhibitor compound, Y. F. C. Lau for providing sequences of the mouse SQR before publication, C. L. Drennan and D. Ringe for the use of computer facilities, and T. Ohnishi, I. Schroder, P. L. Dutton, H. B. Gray, and R. A. Marcus for enlightening discussions.", "abstract": "The quinol-fumarate reductase (QFR) respiratory complex of Escherichia coli is a four-subunit integral-membrane complex that catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. The membrane-soluble redox-active molecule menaquinol (MQH(2)) transfers electrons to QFR by binding directly to the membrane-spanning region. The crystal structure of QFR contains two quinone species, presumably MQH(2), bound to the transmembrane-spanning region. The binding sites for the two quinone molecules are termed Q(P) and Q(D), indicating their positions proximal Q(P)) or distal (Q(D)) to the site of fumarate reduction in the hydrophilic flavoprotein and iron-sulfur protein subunits. It has not been established whether both of these sites are mechanistically significant. Co-crystallization studies of the E. coli QFR with the known quinol-binding site inhibitors 2-heptyl-4-hydroxyquinoline-N-oxide and 2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol establish that both inhibitors block the binding of MQH(2) at the Q(P) site. In the structures with the inhibitor bound at Q(P), no density is observed at Q(D), which suggests that the occupancy of this site can vary and argues against a structurally obligatory role for quinol binding to Q(D). A comparison of the Q(P) site of the E. coli enzyme with quinone-binding sites in other respiratory enzymes shows that an acidic residue is structurally conserved. This acidic residue, Glu-C29, in the E. coli enzyme may act as a proton shuttle from the quinol during enzyme turnover.", "date": "2002-05-03", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "277", "number": "18", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "16124-16130", "id_number": "CaltechAUTHORS:IVEjbc02", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:IVEjbc02", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1074/jbc.M200815200", "primary_object": { "basename": "IVEjbc02.pdf", "url": "https://authors.library.caltech.edu/records/5mcyw-r5876/files/IVEjbc02.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Iverson, Tina M.; Luna-Chavez, C\u00e9sar; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hcx12-at469", "eprint_id": 51860, "eprint_status": "archive", "datestamp": "2023-08-19 09:20:34", "lastmod": "2023-10-18 18:03:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schmid-B", "name": { "family": "Schmid", "given": "Benedikt" } }, { "id": "Ribbe-M-W", "name": { "family": "Ribbe", "given": "Markus W." } }, { "id": "Einsle-O", "name": { "family": "Einsle", "given": "Oliver" } }, { "id": "Yoshida-M", "name": { "family": "Yoshida", "given": "Mika" } }, { "id": "Thomas-L-M", "name": { "family": "Thomas", "given": "Leonard M." } }, { "id": "Dean-D-R", "name": { "family": "Dean", "given": "Dennis R." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Burgess-B-K", "name": { "family": "Burgess", "given": "Barbara K." } } ] }, "title": "Structure of a Cofactor-Deficient Nitrogenase MoFe Protein", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2002 American Association for the Advancement of Science.\n\n18 January 2002; accepted 12 March 2002.\n\nThis work was supported by NIH (B.K.B, D.R.D., and D.C.R.) and by a Deutsche Forschungsgemeinschaft research fellowship (B.S.). The rotation camera facility at the Stanford Synchrotron Radiation Laboratory is supported by the U.S. Department of Energy and NIH. Coordinates have been deposited with the Protein Data Bank (accession code 1L5H). Dedicated to\nthe memory of Barbara K. Burgess (1 January 1951 to 30 December 2001).\n\nSupplemental Material - 1070010s1a.mov
Supplemental Material - 1070010s1b.mov
", "abstract": "One of the most complex biosynthetic processes in metallobiochemistry is the assembly of nitrogenase, the key enzyme in biological nitrogen fixation. We describe here the crystal structure of an iron-molybdenum cofactor\u2013deficient form of the nitrogenase MoFe protein, into which the cofactor is inserted in the final step of MoFe protein assembly. The MoFe protein folds as a heterotetramer containing two copies each of the homologous \u03b1 and \u03b2 subunits. In this structure, one of the three \u03b1 subunit domains exhibits a substantially changed conformation, whereas the rest of the protein remains essentially unchanged. A predominantly positively charged funnel is revealed; this funnel is of sufficient size to accommodate insertion of the negatively charged cofactor.", "date": "2002-04-12", "date_type": "published", "publication": "Science", "volume": "296", "number": "5566", "publisher": "American Association for the Advancement of Science", "pagerange": "352-356", "id_number": "CaltechAUTHORS:20141117-141452827", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141117-141452827", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Deutsche Forschungsgemeinschaft (DFG)" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH" } ] }, "doi": "10.1126/science.1070010", "primary_object": { "basename": "1070010s1a.mov", "url": "https://authors.library.caltech.edu/records/hcx12-at469/files/1070010s1a.mov" }, "related_objects": [ { "basename": "1070010s1b.mov", "url": "https://authors.library.caltech.edu/records/hcx12-at469/files/1070010s1b.mov" } ], "resource_type": "article", "pub_year": "2002", "author_list": "Schmid, Benedikt; Ribbe, Markus W.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/w96ep-6vv77", "eprint_id": 53401, "eprint_status": "archive", "datestamp": "2023-08-21 22:17:26", "lastmod": "2023-10-19 14:50:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Robertson-A-D", "name": { "family": "Robertson", "given": "Andrew D." } } ] }, "title": "Some Thermodynamic Implications for the Thermostability of Proteins", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Protein stability; thermal expansion; protein volumes; stability curve", "note": "\u00a9 2001 The Protein Society.\n\nReceived January 16, 2001; Final Revision March 15, 2001; Accepted March 15, 2001.\n\nThis work was supported in part by National Institutes of General\nMedical Sciences grants GM45162 to D.C.R. and GM46869 to\nA.D.R. The publication costs of this article were defrayed in part\nby payment of page charges. This article must therefore be hereby\nmarked \"advertisement\" in accordance with 18 USC section 1734\nsolely to indicate this fact.", "abstract": "An analysis of the thermodynamics of protein stability reveals a general tendency for proteins that denature\nat higher temperatures to have greater free energies of maximal stability. To a reasonable approximation, the\ntemperature of maximal stability for the set of globular, water-soluble proteins surveyed by Robertson and\nMurphy occurs at T* \u223c283K, independent of the heat denaturation temperature, T_m. This observation\nindicates, at least for these proteins, that thermostability tends to be achieved through elevation of the\nstability curve rather than by broadening or through a horizontal shift to higher temperatures. The relationship\nbetween the free energy of maximal stability and the temperature of heat denaturation is such that an\nincrease in maximal stability of \u223c0.008 kJ/mole/residue is, on average, associated with a 1\u00b0C increase in T_m.\nAn estimate of the energetic consequences of thermal expansion suggests that these effects may contribute\nsignificantly to the destabilization of the native state of proteins with increasing temperature.", "date": "2001-06", "date_type": "published", "publication": "Protein Science", "volume": "10", "number": "6", "publisher": "Wiley", "pagerange": "1187-1194", "id_number": "CaltechAUTHORS:20150108-153227470", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-153227470", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Institutes of General Medical Sciences", "grant_number": "GM45162" }, { "agency": "National Institutes of General Medical Sciences", "grant_number": "GM46869" } ] }, "doi": "10.1110/ps.180101", "pmcid": "PMC2374017", "resource_type": "article", "pub_year": "2001", "author_list": "Rees, Douglas C. and Robertson, Andrew D." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1bexd-q1z47", "eprint_id": 53409, "eprint_status": "archive", "datestamp": "2023-08-21 22:08:41", "lastmod": "2023-10-19 14:50:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chiu-H-J", "name": { "family": "Chiu", "given": "Hsiu-Ju" } }, { "id": "Johnson-E", "name": { "family": "Johnson", "given": "Eric" } }, { "id": "Schr\u00f6der-I", "name": { "family": "Schr\u00f6der", "given": "Imke" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structures of a Novel Ferric Reductase from the Hyperthermophilic Archaeon Archaeoglobus fulgidus and Its Complex with NADP+", "ispublished": "pub", "full_text_status": "restricted", "keywords": "ferric reductase; flavoproteins; ferredoxin reductase superfamily; iron metabolism; NAD(P)H:flavin oxidoreductase", "note": "\u00a9 2001 Elsevier Science Ltd.\n\nReceived: December 18, 2000;\nRevised: January 31, 2001;\nAccepted: February 20, 2001.\n\nWe thank the reviewers for their insightful comments. This work was supported by National Institutes of Health HL-16251 (I. S.) and National Institutes of Health GM-45162 (D. C. R). This work is based on research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL), which is funded by the Department of Energy, Office of Basic Energy Sciences, and the National Institutes of Health.", "abstract": "Background: Studies performed within the last decade have indicated that microbial reduction of Fe(III) to Fe(II) is a biologically significant process. The ferric reductase (FeR) from Archaeoglobus fulgidus is the first reported archaeal ferric reductase and it catalyzes the flavin-mediated reduction of ferric iron complexes using NAD(P)H as the electron donor. Based on its catalytic activity, the A. fulgidus FeR resembles the bacterial and eukaryotic assimilatory type of ferric reductases. However, the high cellular abundance of the A. fulgidus FeR (\u223c0.75% of the total soluble protein) suggests a catabolic role for this enzyme as the terminal electron acceptor in a ferric iron\u2013based respiratory pathway [1].\n\nResults: The crystal structure of recombinant A. fulgidus FeR containing a bound FMN has been solved at 1.5 \u00c5 resolution by multiple isomorphous replacement/anomalous diffraction (MIRAS) phasing methods, and the NADP+- bound complex of FeR was subsequently determined at 1.65 \u00c5 resolution. FeR consists of a dimer of two identical subunits, although only one subunit has been observed to bind the redox cofactors. Each subunit is organized around a six-stranded antiparallel \u03b2 barrel that is homologous to the FMN binding protein from Desulfovibrio vulgaris. This fold has been shown to be related to a circularly permuted version of the flavin binding domain of the ferredoxin reductase superfamily. The A. fulgidus ferric reductase is further distinguished from the ferredoxin reductase superfamily by the absence of a Rossmann fold domain that is used to bind the NAD(P)H. Instead, FeR uses its single domain to provide both the flavin and the NAD(P)H binding sites. Potential binding sites for ferric iron complexes are identified near the cofactor binding sites.\n\nConclusions: The work described here details the structures of the enzyme-FMN, enzyme-FMN-NADP+, and possibly the enzyme-FMN-iron intermediates that are present during the reaction mechanism. This structural information helps identify roles for specific residues during the reduction of ferric iron complexes by the A. fulgidus FeR.", "date": "2001-04-07", "date_type": "published", "publication": "Structure", "volume": "9", "number": "4", "publisher": "Cell Press", "pagerange": "311-319", "id_number": "CaltechAUTHORS:20150108-153854607", "issn": "0969-2126", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-153854607", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "HL-16251" }, { "agency": "NIH", "grant_number": "GM-45162" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH" } ] }, "doi": "10.1016/S0969-2126(01)00589-5", "resource_type": "article", "pub_year": "2001", "author_list": "Chiu, Hsiu-Ju; Johnson, Eric; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/mpn2m-ayn37", "eprint_id": 53404, "eprint_status": "archive", "datestamp": "2023-08-21 22:07:08", "lastmod": "2023-10-19 14:50:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Arciero-D-M", "name": { "family": "Arciero", "given": "David M." } }, { "id": "Hooper-A-B", "name": { "family": "Hooper", "given": "Alan B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "High-Resolution Structures of the Oxidized and Reduced States of Cytochrome c554 from Nitrosomonas europaea", "ispublished": "pub", "full_text_status": "restricted", "keywords": "cytochrome; heme; nitrification; porphyrin; Nitrosomonas europaea", "note": "\u00a9 2001 SBIC.\n\nReceived 27 October 2000; Accepted 11 January 2001; Published online 28 March 2011.\n\nWe thank R. Dieckmann, J. Chiu, and F.A. Tezcan for experimental assistance and J.A. Shelnutt for calculations of the distortions of the porphyrins. This work was supported by an NSF grant (MCB-9723608) to A.B.H. and an NIH grant (GM45162) to D.C.R. T.M.I. was supported by an NIH fellowship (GM07737). This work is based upon research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL), which is funded by the Department of Energy, Office of Basic Energy Sciences.", "abstract": "Cytochrome c554 (cyt c554) is a tetra-heme cytochrome involved in the oxidation of NH3 by Nitrosomonas europaea. The X-ray crystal structures of both the oxidized and dithionite-reduced states of cyt c554 in a new, rhombohedral crystal form have been solved by molecular replacement, at 1.6 \u00c5 and 1.8 \u00c5 resolution, respectively. Upon reduction, the conformation of the polypeptide chain changes between residues 175 and 179, which are adjacent to hemes III and IV. Cyt c554 displays conserved heme-packing motifs that are present in other heme-containing proteins. Comparisons to hydroxylamine oxidoreductase, the electron donor to cyt c554, and cytochrome c nitrite reductase, an enzyme involved in nitrite ammonification, reveal substantial structural similarity in the polypeptide chain surrounding the heme core environment. The structural determinants of these heme-packing motifs extend to the buried water molecules that hydrogen bond to the histidine ligands to the heme iron. In the original structure determination of a tetragonal crystal form, a cis peptide bond between His129 and Phe130 was identified that appeared to be stabilized by crystal contacts. In the rhombohedral crystal form used in the present high-resolution structure determination, this peptide bond adopts the trans conformation, but with disallowed angles of \u03c6 and \u03c8.", "date": "2001-04", "date_type": "published", "publication": "Journal of Biological Inorganic Chemistry", "volume": "6", "number": "4", "publisher": "Springer", "pagerange": "390-397", "id_number": "CaltechAUTHORS:20150108-153416410", "issn": "0949-8257", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-153416410", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-9723608" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "GM07737" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1007/s007750100213", "resource_type": "article", "pub_year": "2001", "author_list": "Iverson, Tina M.; Arciero, David M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hvka1-7xm10", "eprint_id": 53408, "eprint_status": "archive", "datestamp": "2023-08-19 07:29:19", "lastmod": "2023-10-19 14:50:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Strop-P", "name": { "family": "Strop", "given": "Pavel" } }, { "id": "Smith-K-S", "name": { "family": "Smith", "given": "Kerry S." } }, { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Ferry-J-G", "name": { "family": "Ferry", "given": "James G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structure of the \"cab\"-type \u03b2 Class Carbonic Anhydrase from the Archaeon Methanobacterium thermoautotrophicum", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2001 by The American Society for Biochemistry and Molecular Biology, Inc.\n\nReceived for publication, October 9, 2000, and in revised form, November 26, 2000. First Published on November 28, 2000.\n\nThis work was supported by National Institutes of Health Grants GM44661 (to J. G. F) and GM45162 (to D. C. R.); a National Science Foundation predoctoral fellowship (to P. S.); and NASA-AMES Cooperative Agreement NCC2-1057 (to the Pennsylvania State University Astrobiology Research Center). This work is based upon research conducted at the Stanford Synchrotron Radiation Laboratory, which is funded by the Department of Energy (Office of Basic Energy Sciences and Office of Biological and Environmental Research) and the National Institutes of Health (National Center for Research Resources, NIGMS).\nThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.\n\nWe thank Jessica Wuu and Radu Georgescu for help with crystallizations and Brian R. Crane and Alex M. Bilwes for help with data collection.", "abstract": "The structure of the \"cab\"-type \u03b2 class carbonic anhydrase from the archaeon Methanobacterium thermoautotrophicum (Cab) has been determined to 2.1-\u00c5 resolution using the multiwavelength anomalous diffraction phasing technique. Cab exists as a dimer with a subunit fold similar to that observed in \"plant\"-type \u03b2 class carbonic anhydrases. The active site zinc is coordinated by protein ligands Cys^(32), His^(87), and Cys^(90), with the tetrahedral coordination completed by a water molecule. The major difference between plant- and cab-type \u03b2 class carbonic anhydrases is in the organization of the hydrophobic pocket. The structure reveals a Hepes buffer molecule bound 8 \u00c5 away from the active site zinc, which suggests a possible proton transfer pathway from the active site to the solvent.", "date": "2001-03-30", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "276", "number": "13", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "10299-10305", "id_number": "CaltechAUTHORS:20150108-153724662", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-153724662", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM44661" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NSF Predoctoral Fellowship" }, { "agency": "NASA", "grant_number": "NCC2-1057" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1074/jbc.M009182200", "resource_type": "article", "pub_year": "2001", "author_list": "Strop, Pavel; Smith, Kerry S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jxq3a-tqr04", "eprint_id": 53406, "eprint_status": "archive", "datestamp": "2023-08-21 22:05:33", "lastmod": "2023-10-19 14:50:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Locher-K-P", "name": { "family": "Locher", "given": "Kaspar P." } }, { "id": "Hans-M", "name": { "family": "Hans", "given": "Marcus" } }, { "id": "Yeh-A-P", "name": { "family": "Yeh", "given": "Andrew P." } }, { "id": "Schmid-B", "name": { "family": "Schmid", "given": "Benedikt" } }, { "id": "Buckel-W", "name": { "family": "Buckel", "given": "Wolfgang" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA Dehydratase Component A", "ispublished": "pub", "full_text_status": "restricted", "keywords": "actin fold; hexokinase; heat shock protein 70; ATP hydrolysis; electron transfer", "note": "\u00a9 2001 Academic Press.\n\nReceived 12 December 2000; received in revised form 25 January 2001; accepted 25 January 2001.\n\nWe thank J. B. Howard for stimulating discussions and National Institutes of Health grant GM45162 to D.C.R. and Deutsche Forschungsgemeinschaft grants to W. B. and to M.H. for support of this research.", "abstract": "Acidaminococcus fermentans degrades glutamate via the hydroxyglutarate pathway, which involves the syn-elimination of water from (R)-2-hydroxyglutaryl-CoA in a key reaction of the pathway. This anaerobic process is catalyzed by 2-hydroxyglutaryl-CoA dehydratase, an enzyme with two components (A and D) that reversibly associate during reaction cycles. Component A (CompA), a homodimeric protein of 2x27 kDa, contains a single, bridging [4Fe-4S] cluster and uses the hydrolysis of ATP to deliver an electron to the dehydratase component (CompD), where the electron is used catalytically. The structure of the extremely oxygen-sensitive CompA protein was solved by X-ray crystallography to 3 \u00c5 resolution. The protein was found to be a member of the actin fold family, revealing a similar architecture and nucleotide-binding site. The key differences between CompA and other members of the actin fold family are: (i) the presence of a cluster binding segment, the \"cluster helix\"; (ii) the [4Fe-4S] cluster; and (iii) the location of the homodimer interface, which involves the bridging cluster. Possible reaction mechanisms are discussed in light of the close structural similarity to members of the actin-fold family and the functional similarity to the nitrogenase Fe-protein.", "date": "2001-03-16", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "307", "number": "1", "publisher": "Elsevier", "pagerange": "297-308", "id_number": "CaltechAUTHORS:20150108-153550607", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-153550607", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)" } ] }, "doi": "10.1006/jmbi.2000.4496", "resource_type": "article", "pub_year": "2001", "author_list": "Locher, Kaspar P.; Hans, Marcus; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ps9se-sf882", "eprint_id": 53411, "eprint_status": "archive", "datestamp": "2023-08-19 07:14:39", "lastmod": "2023-10-19 14:50:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Strop-P", "name": { "family": "Strop", "given": "Pavel" } }, { "id": "Takahara-P-M", "name": { "family": "Takahara", "given": "Patricia M." } }, { "id": "Chiu-H-J", "name": { "family": "Chiu", "given": "Hsiu-Ju" } }, { "id": "Angove-H-C", "name": { "family": "Angove", "given": "Hayley C." } }, { "id": "Burgess-B-K", "name": { "family": "Burgess", "given": "Barbara K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structure of the All-ferrous [4Fe-4S]^0 Form of the Nitrogenase Iron Protein from Azotobacter vinelandii", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2001 American Chemical Society.\n\nReceived July 14, 2000; Revised Manuscript Received November 7, 2000.\nPublication Date (Web): December 21, 2000.\n\nThis work was supported by the National Institute of Health (Grant\nGM43144 to B.K.B. and Grant GM45162 to D.C.R.), an NSF graduate\nfellowship (P.S.), and an NSF postdoctoral fellowship (P.M.T.). This\nwork is based upon research conducted at the Stanford Synchrotron\nRadiation Laboratory (SSRL), which is funded by the Department of\nEnergy (BES and BER) and the National Institutes of Health (NCRR\nand NIGMS). The Advanced Light Source is supported by the Director,\nOffice of Energy Research, Office of Basic Energy Sciences, Materials\nSciences Division, of the U.S. Department of Energy under Contract\nDE-AC03-76SF00098 at Lawrence Berkeley National Laboratory.\n\nWe thank Tina M. Iverson for assistance with data\ncollection and James B. Howard for discussions.", "abstract": "The structure of the nitrogenase iron protein from Azotobacter vinelandii in the all-ferrous [4Fe-4S]^0 form has been determined to 2.25 \u00c5 resolution by using the multiwavelength anomalous diffraction (MAD) phasing technique. The structure demonstrates that major conformational changes are not necessary either in the iron protein or in the cluster to accommodate cluster reduction to the [4Fe-4S]^0 oxidation state. A survey of [4Fe-4S] clusters coordinated by four cysteine ligands in proteins of known structure reveals that the [4Fe-4S] cluster of the iron protein has the largest accessible surface area, suggesting that solvent exposure may be relevant to the ability of the iron protein to exist in three oxidation states.", "date": "2001-01-23", "date_type": "published", "publication": "Biochemistry", "volume": "40", "number": "3", "publisher": "American Chemical Society", "pagerange": "651-656", "id_number": "CaltechAUTHORS:20150108-154148325", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154148325", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM43144" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NSF Graduate Fellowship" }, { "agency": "NSF Postdoctoral Fellowship" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC03-76SF00098" } ] }, "doi": "10.1021/bi0016467", "resource_type": "article", "pub_year": "2001", "author_list": "Strop, Pavel; Takahara, Patricia M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p4f7e-kg414", "eprint_id": 53400, "eprint_status": "archive", "datestamp": "2023-08-19 06:58:31", "lastmod": "2024-01-13 16:13:29", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystallographic Analyses of Hyperthermophilic Proteins", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2001 by Academic Press.\n\nHeated discussions with co-workers and collaborators, particularly M. W. W. Adams and J. B. Howard, are gratefully acknowledged. This work was supported by the Howard Hughes Medical Institute and the National Institutes of Health (GM45162).", "abstract": "Following the first structure determination in 1992 of a protein from a hyperthermophilic\norganism, the rubredoxin from Pyrococcus furiosus, structures of\nhyperthermophilic proteins have appeared at an ever increasing rate, with more\nthan 50 distinct structures having been submitted to the Protein Data Bank as\nof October 1999 (Table I). These structure determinations have been undertaken\nfor many of the reasons discussed elsewhere in this volume-to understand the\nstructural basis of thermostability; to more fully characterize proteins with unusual\ncofactors or active centers; for biotechnological purposes; as homologs of eukaryotic\nproteins, especially those involved in some aspect of macromolecular biosynthesis;\nand as part of structural genomics efforts, because they either do, or do not,\nlook like some other proteins. As there is an expectation that hyperthermostable\nproteins should be more robust and potentially better suited for withstanding the\nsolution conditions and time scales of crystallization experiments, these proteins\nhave provided attractive targets for structural studies. The focus of this chapter\nis to review the status and some general implications of crystallographic studies\non hyperthermophilic proteins, with emphasis on relevant technical aspects of\nthe structure determination, quality of the crystals, and conclusions about thermal\nstability and other properties of these fascinating proteins.", "date": "2001", "date_type": "published", "publisher": "Academic Press", "place_of_pub": "San Diego, CA", "pagerange": "423-437", "id_number": "CaltechAUTHORS:20150108-153028358", "isbn": "978-0-12-182235-4", "book_title": "Hyperthermophilic Enzymes, Part C", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-153028358", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "contributors": { "items": [ { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Kelly-R-M", "name": { "family": "Kelly", "given": "Robert M." } } ] }, "doi": "10.1016/S0076-6879(01)34484-1", "resource_type": "book_section", "pub_year": "2001", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/q3kmz-bpj77", "eprint_id": 47553, "eprint_status": "archive", "datestamp": "2023-08-19 06:54:48", "lastmod": "2023-10-26 20:42:17", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chiu-H-J", "name": { "family": "Chiu", "given": "Hsiu-Ju" } }, { "id": "Peters-J-W", "name": { "family": "Peters", "given": "John W." } }, { "id": "Lanzilotta-W-N", "name": { "family": "Lanzilotta", "given": "William N." } }, { "id": "Ryle-M-J", "name": { "family": "Ryle", "given": "Matthew J." } }, { "id": "Seefeldt-L-C", "name": { "family": "Seefeldt", "given": "Lance C." } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "MgATP-Bound and Nucleotide-Free Structures of a Nitrogenase Protein Complex between the Leu 127\u0394-Fe-Protein and the MoFe-Protein", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2001 American Chemical Society. Received July 14, 2000; Revised Manuscript; Received November 7, 2000. This work was supported by NIH Grant GM45162 (D.C.R. and J.B.H.), NSF Grant MCB 9722937 (L.C.S.), and NIH Postdoctoral Fellowship GM18142 (J.W.P.). The rotation camera facility at the Stanford Synchrotron Radiation Laboratory is supported by the Department of Energy Office of Basic Sciences and the NIH Biomedical Technology Program, Division of Research Resources.", "abstract": "A mutant form of the nitrogenase iron protein with a deletion of residue Leu 127, located in the switch II region of the nucleotide binding site, forms a tight, inactive complex with the nitrogenase molybdenum iron (MoFe) protein in the absence of nucleotide. The structure of this complex generated with proteins from Azotobacter vinelandii (designated the L127\u0394-Av2\u2212Av1 complex) has been crystallographically determined in the absence of nucleotide at 2.2 \u00c5 resolution and with bound MgATP (introduced by soaking) at 3.0 \u00c5 resolution. As observed in the structure of the complex between the wild-type A. vinelandii nitrogenase proteins stabilized with ADP\u00b7AlF_4^-, the most significant conformational changes in the L127\u0394 complex occur in the Fe-protein component. While the interactions at the interface between the MoFe-protein and Fe-proteins are conserved in the two complexes, significant differences are evident at the subunit\u2212subunit interface of the dimeric Fe-proteins, with the L127\u0394-Av2 structure having a more open conformation than the wild-type Av2 in the complex stabilized by ADP\u00b7AlF_4^-. Addition of MgATP to the L127\u0394-Av2\u2212Av1 complex results in a further increase in the separation between Fe-protein subunits so that the structure more closely resembles that of the wild-type, nucleotide-free, uncomplexed Fe-protein, rather than the Fe-protein conformation in the ADP\u00b7AlF_4^- complex. The L127\u0394 mutation precludes key interactions between the Fe-protein and nucleotide, especially, but not exclusively, in the region corresponding to the switch II region of G-proteins, where the deletion constrains Gly 128 and Asp 129 from forming hydrogen bonds to the \u03b3-phosphate and activating water for attack on this group, respectively. These alterations account for the inability of this mutant to support mechanistically productive ATP hydrolysis. The ability of the L127\u0394-Av2\u2212Av1 complex to bind MgATP demonstrates that dissociation of the nitrogenase complex is not required for nucleotide binding.", "date": "2000-12-21", "date_type": "published", "publication": "Biochemistry", "volume": "40", "number": "3", "publisher": "American Chemical Society", "pagerange": "641-650", "id_number": "CaltechAUTHORS:20140729-102140505", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140729-102140505", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NSF", "grant_number": "MCB 9722937" }, { "agency": "NIH", "grant_number": "GM18142" }, { "agency": "Department of Energy (DOE) Office of Basic Sciences" } ] }, "doi": "10.1021/bi001645e", "resource_type": "article", "pub_year": "2000", "author_list": "Chiu, Hsiu-Ju; Peters, John W.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z0qmn-wjr62", "eprint_id": 53412, "eprint_status": "archive", "datestamp": "2023-08-21 21:37:03", "lastmod": "2023-10-19 14:51:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } } ] }, "title": "Nitrogenase: Standing at the Crossroads", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Nitrogenase; EPR; Metalloclusters; FE protein; MoFe protein; Enzyme mechanism", "note": "\u00a9 2000 Elsevier Science Ltd.\n\nDiscussions with members of our groups and nitrogenase colleagues are\ngreatly appreciated. Research in the authors' laboratory was supported by\nUnited States Public Health Service grant GM45162 (DCR and JBH) and\nNational Science Foundation MCB9513512 (JBH).", "abstract": "Nitrogenase catalyzes the ATP-dependent reduction of dinitrogen to ammonia, which is central to the process of biological nitrogen fixation. Recent progress towards establishing the mechanism of action of this complex metalloenzyme reflects the contributions of a combination of structural, biochemical, spectroscopic, synthetic and theoretical approaches to a challenging problem with implications for a range of biochemical and chemical systems.", "date": "2000-10", "date_type": "published", "publication": "Current Opinion in Chemical Biology", "volume": "4", "number": "5", "publisher": "Elsevier", "pagerange": "559-566", "id_number": "CaltechAUTHORS:20150108-154309553", "issn": "1367-5931", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154309553", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "USPHS", "grant_number": "GM45162" }, { "agency": "NSF", "grant_number": "MCB9513512" } ] }, "doi": "10.1016/S1367-5931(00)00132-0", "resource_type": "article", "pub_year": "2000", "author_list": "Rees, Douglas C. and Howard, James B." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zmeng-s9w48", "eprint_id": 53415, "eprint_status": "archive", "datestamp": "2023-08-19 06:11:02", "lastmod": "2023-10-19 14:51:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Alber-B-E", "name": { "family": "Alber", "given": "Birgit E." } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Ferry-J-G", "name": { "family": "Ferry", "given": "James G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A Closer Look at the Active Site of \u03b3-Class Carbonic Anhydrases: High-Resolution Crystallographic Studies of the Carbonic Anhydrase from Methanosarcina thermophila", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2000 American Chemical Society.\n\nReceived February 1, 2000; Revised Manuscript Received May 12, 2000.\n\nThis work was supported by a grant from the National Institutes\nof Health to J.G.F. (GM44661). T.M.I. is supported by a NIH training\ngrant (GM07737).\n\nWe are grateful to C. Fierke, D. Silverman, and R. Cheng\nfor critical reading and helpful discussions, B. Tripp for\nunpublished results, and H. Schindelin for experimental\nassistance. This work is based upon research conducted at\nthe Stanford Synchrotron Radiation Laboratory (SSRL),\nwhich is funded by the Department of Energy, Office of\nBasic Energy Sciences.", "abstract": "The prototype of the \u03b3-class of carbonic anhydrase has been characterized from the methanogenic archaeon Methanosarcina thermophila. Previously reported kinetic studies of the \u03b3-class carbonic anhydrase are consistent with this enzyme having a reaction mechanism similar to that of the mammalian \u03b1-class carbonic anhydrase. However, the overall folds of these two enzymes are dissimilar, and apart from the zinc-coordinating histidines, the active site residues bear little resemblance to one another. The crystal structures of zinc-containing and cobalt-substituted \u03b3-class carbonic anhydrases from M. thermophila are reported here between 1.46 and 1.95 \u00c5 resolution in the unbound form and cocrystallized with either SO_4^2- or HCO_3^-. Relative to the tetrahedral coordination geometry seen at the active site in the \u03b1-class of carbonic anhydrases, the active site of the \u03b3-class enzyme contains additional metal-bound water ligands, so the overall coordination geometry is trigonal bipyramidal for the zinc-containing enzyme and octahedral for the cobalt-substituted enzyme. Ligands bound to the active site all make contacts with the side chain of Glu 62 in manners that suggest the side chain is likely protonated. In the uncomplexed zinc-containing enzyme, the side chains of Glu 62 and Glu 84 appear to share a proton; additionally, Glu 84 exhibits multiple conformations. This suggests that Glu 84 may act as a proton shuttle, which is an important aspect of the reaction mechanism of \u03b1-class carbonic anhydrases. A hydrophobic pocket on the surface of the enzyme may participate in the trapping of CO2 at the active site. On the basis of the coordination geometry at the active site, ligand binding modes, the behavior of the side chains of Glu 62 and Glu 84, and analogies to the well-characterized \u03b1-class of carbonic anhydrases, a more-defined reaction mechanism is proposed for the \u03b3-class of carbonic anhydrases.", "date": "2000-08-08", "date_type": "published", "publication": "Biochemistry", "volume": "39", "number": "31", "publisher": "American Chemical Society", "pagerange": "9222-9231", "id_number": "CaltechAUTHORS:20150108-154703618", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154703618", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM44661" }, { "agency": "NIH", "grant_number": "GM07737" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1021/bi000204s", "resource_type": "article", "pub_year": "2000", "author_list": "Iverson, Tina M.; Alber, Birgit E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wmk4z-8dh06", "eprint_id": 53414, "eprint_status": "archive", "datestamp": "2023-08-21 21:26:08", "lastmod": "2023-10-19 14:51:16", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Luna-Chavez-C", "name": { "family": "Luna-Chavez", "given": "C\u00e9sar" } }, { "id": "Schr\u00f6der-I", "name": { "family": "Schr\u00f6der", "given": "Imke" } }, { "id": "Cecchini-G", "name": { "family": "Cecchini", "given": "Gary" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Analyzing Your Complexes: Structure of the Quinol-Fumarate Reductase Respiratory Complex", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Quinol fumarate reductase; Succinate quinone oxidoreductase; Succinate dehydrogenase; Complex II; Respiratory complexes; Flavoenzymes; Iron-sulfur proteins; Fumarate reductase; Membrane protein structure; Energy transduction", "note": "\u00a9 2000 Elsevier Science Ltd.\n\nThis work has been supported by the Department of Veterans Affairs\n(GC) and funding from the Howard Hughes Medical Institute (DCR),\nNational Institutes of Health grants GM45162 (DCR) and HL-16251\n(GC), and National Science Foundation grant MCB-9729778 (GC). We\nwould like to acknowledge stimulating discussions with T Ohnishi, PL\nDutton, HB Gray and S Iwata.", "abstract": "The integral membrane protein complex quinol-fumarate reductase catalyzes the terminal step of a major anaerobic respiratory pathway. The homologous enzyme succinate-quinone oxidoreductase participates in aerobic respiration both as complex II and as a member of the Krebs cycle. Last year, two structures of quinol-fumarate reductases were reported. These structures revealed the cofactor organization linking the fumarate and quinol sites, and showed a cofactor arrangement across the membrane that is suggestive of a possible energy coupling function.", "date": "2000-08", "date_type": "published", "publication": "Current Opinion in Structural Biology", "volume": "10", "number": "4", "publisher": "Elsevier", "pagerange": "448-455", "id_number": "CaltechAUTHORS:20150108-154546091", "issn": "0959-440X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154546091", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Veterans Affairs" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "HL-16251" }, { "agency": "NSF", "grant_number": "MCB-9729778" } ] }, "doi": "10.1016/S0959-440X(00)00113-5", "resource_type": "article", "pub_year": "2000", "author_list": "Iverson, Tina M.; Luna-Chavez, C\u00e9sar; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/w6bp8-7k191", "eprint_id": 53413, "eprint_status": "archive", "datestamp": "2023-08-21 21:23:12", "lastmod": "2023-10-19 14:51:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeh-A-P", "name": { "family": "Yeh", "given": "Andrew P." } }, { "id": "Chatelet-C", "name": { "family": "Chatelet", "given": "Claire" } }, { "id": "Soltis-S-M", "name": { "family": "Soltis", "given": "S. Michael" } }, { "id": "Kuhn-P", "name": { "family": "Kuhn", "given": "Peter" } }, { "id": "Meyer-J", "name": { "family": "Meyer", "given": "Jacques" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of a Thioredoxin-like [2Fe-2S] Ferredoxin from Aquifex aeolicus", "ispublished": "pub", "full_text_status": "restricted", "keywords": "crystal structure; [2Fe-2S] ferredoxin; thioredoxin; respiratory chain; iron-sulfur clusters", "note": "\u00a9 2000 Academic Press.\n\nReceived 29 March 2000; received in revised form 12 May 2000; accepted 15 May 2000.\n\nWe thank the National Institutes of Health (D.C.R.)\nfor support. A.P.Y. was supported in part by a National\nScience Foundation Graduate Research Fellowship. This\nwork is based upon research conducted at the Stanford\nSynchrotron Radiation Laboratory (SSRL), which is\nfunded by the Department of Energy, Office of Basic\nEnergy Sciences. The Biotechnology Program is supported\nby the National Institutes of Health, National\nCenter for Research Resources, Biomedical Technology\nProgram and the Department of Energy, Office of\nBiological and Environmental Research.", "abstract": "The 2.3 \u00c5 resolution crystal structure of a [2Fe-2S] cluster containing ferredoxin from Aquifex aeolicusreveals a thioredoxin-like fold that is novel among iron-sulfur proteins. The [2Fe-2S] cluster is located near the surface of the protein, at a site corresponding to that of the active-site disulfide bridge in thioredoxin. The four cysteine ligands are located near the ends of two surface loops. Two of these ligands can be substituted by non-native cysteine residues introduced throughout a stretch of the polypeptide chain that forms a protruding loop extending away from the cluster. The presence of homologs of this ferredoxin as components of more complex anaerobic and aerobic electron transfer systems indicates that this is a versatile fold for biological redox processes.", "date": "2000-07-14", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "300", "number": "3", "publisher": "Elsevier", "pagerange": "587-595", "id_number": "CaltechAUTHORS:20150108-154426156", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154426156", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1006/jmbi.2000.3871", "resource_type": "article", "pub_year": "2000", "author_list": "Yeh, Andrew P.; Chatelet, Claire; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/m44fk-58p80", "eprint_id": 53416, "eprint_status": "archive", "datestamp": "2023-08-19 05:30:14", "lastmod": "2023-10-19 14:51:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeh-A-P", "name": { "family": "Yeh", "given": "Andrew P." } }, { "id": "Hu-Yonglin", "name": { "family": "Hu", "given": "Yonglin" } }, { "id": "Jenney-F-E-Jr", "name": { "family": "Jenney", "given": "Francis E., Jr." } }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structures of the Superoxide Reductase from Pyrococcus furiosus in the Oxidized and Reduced States", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2000 American Chemical Society.\n\nReceived October 19, 1999; Revised Manuscript Received December 22, 1999.\nPublication Date (Web): February 16, 2000.\n\nThis work was supported in part by grants from the Department\nof Energy (FG05-95ER20175) and the National Science Foundation\n(MCB 9809060) to M.W.W.A. and from the National Institutes of\nHealth (GM45162) to D.C.R. A.P.Y. was supported in part by a\nNational Science Foundation Graduate Research Fellowship. The\nprotein crystallographic facility at the Stanford Synchrotron Radiation\nLaboratory (SSRL) is funded by the Department of Energy, Office of\nBasic Energy Sciences, the National Institutes of Health, National\nCenter for Research Resources, Biomedical Technology Program, and\nthe Department of Energy, Office of Biological and Environmental\nResearch.\n\nWe greatly appreciate the contributions of Caroline Kisker,\nHong Li, Hermann Schindelin, and Xiao-Dong Su to the\nstructure determination.", "abstract": "Superoxide reductase (SOR) is a blue non-heme iron protein that functions in anaerobic microbes as a defense mechanism against reactive oxygen species by catalyzing the reduction of superoxide to hydrogen peroxide [Jenney, F. E., Jr., Verhagen, M. F. J. M., Cui, X., and Adams, M. W. W. (1999) Science 286, 306\u2212309]. Crystal structures of SOR from the hyperthermophilic archaeon Pyrococcus furiosus have been determined in the oxidized and reduced forms to resolutions of 1.7 and 2.0 \u00c5, respectively. SOR forms a homotetramer, with each subunit adopting an immunoglobulin-like \u03b2-barrel fold that coordinates a mononuclear, non-heme iron center. The protein fold and metal center are similar to those observed previously for the homologous protein desulfoferrodoxin from Desulfovibrio desulfuricans [Coelho, A. V., Matias, P., F\u00fcl\u00f6p, V., Thompson, A., Gonzalez, A., and Carrondo, M. A. (1997) J. Bioinorg. Chem. 2, 680\u2212689]. Each iron is coordinated to imidazole nitrogens of four histidines in a planar arrangement, with a cysteine ligand occupying an axial position normal to this plane. In two of the subunits of the oxidized structure, a glutamate carboxylate serves as the sixth ligand to form an overall six-coordinate, octahedral coordinate environment. In the remaining two subunits, the sixth coordination site is either vacant or occupied by solvent molecules. The iron centers in all four subunits of the reduced structure exhibit pentacoordination. The structures of the oxidized and reduced forms of SOR suggest a mechanism by which superoxide accessibility may be controlled and define a possible binding site for rubredoxin, the likely physiological electron donor to SOR.", "date": "2000-03-14", "date_type": "published", "publication": "Biochemistry", "volume": "39", "number": "10", "publisher": "American Chemical Society", "pagerange": "2499-2508", "id_number": "CaltechAUTHORS:20150108-154842858", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154842858", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)", "grant_number": "FG05-95ER20175" }, { "agency": "NSF", "grant_number": "MCB 9809060" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "doi": "10.1021/bi992428k", "resource_type": "article", "pub_year": "2000", "author_list": "Yeh, Andrew P.; Hu, Yonglin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2ggje-dzt59", "eprint_id": 53417, "eprint_status": "archive", "datestamp": "2023-08-21 20:56:27", "lastmod": "2023-10-19 14:51:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kielkopf-C-L", "name": { "family": "Kielkopf", "given": "Clara L." } }, { "id": "Ding-S", "name": { "family": "Ding", "given": "Sheng" } }, { "id": "Kuhn-P", "name": { "family": "Kuhn", "given": "Peter" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Conformational Flexibility of B-DNA at 0.74 \u00c5 Resolution: d(CCAGTACTGG)_2", "ispublished": "pub", "full_text_status": "restricted", "keywords": "B-DNA; DNA structure; ultrahigh resolution; nucleic acid structure; calcium binding", "note": "\u00a9 2000 Academic Press.\n\nReceived 1 November 1999; received in revised form 17 December 1999; accepted 18 December 1999.\n\nWe are grateful to the NIH for research support and\nto the NSF and NIH for predoctoral fellowships to\nC.L.K. We thank R. Bau for assistance with the refinement,\nS. Horvath for oligonucleotide synthesis, Leemor\nJoshua-Tor, Eldon Baird and members of the Dervan and\nBarton groups for discussions. This work is based in part\non research conducted at the Stanford Synchrotron Radiation\nLaboratory, which is funded by the Department of\nEnergy (BES, OBER) and the National Institutes of\nHealth (NCRR, NIGMS).", "abstract": "The affinity and specificity of a ligand for its DNA site is a function of the conformational changes between the isolated and complexed states. Although the structures of a hydroxypyrrole-imidazole-pyrrole polyamide dimer with 5\u2032-CCAGTACTGG-3\u2032 and the trp repressor recognizing the sequence 5\u2032-GTACT-3\u2032 are known, the baseline conformation of the DNA site would contribute to our understanding of DNA recognition by these ligands. The 0.74 \u00c5 resolution structure of a B-DNA double helix, 5\u2032-CCAGTACTGG-3\u2032, has been determined by X-ray crystallography. Six of the nine phosphates, two of four bound calcium ions and networks of water molecules hydrating the oligonucleotide have alternate conformations. By contrast, nine of the ten bases have a single, unique conformation with hydrogen atoms visible in most cases. The polyamide molecules alter the geometry of the phosphodiester backbone, and the water molecules mediating contacts in the trp repressor/operator complex are conserved in the unliganded DNA. Furthermore, the multiple conformational states, ions and hydration revealed by this ultrahigh resolution structure of a B-form oligonucleotide are potentially general considerations for understanding DNA-binding affinity and specificity by ligands.", "date": "2000-02-25", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "296", "number": "3", "publisher": "Elsevier", "pagerange": "787-801", "id_number": "CaltechAUTHORS:20150108-154955030", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-154955030", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1006/jmbi.1999.3478", "resource_type": "article", "pub_year": "2000", "author_list": "Kielkopf, Clara L.; Ding, Sheng; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/nqsd7-pxx36", "eprint_id": 53418, "eprint_status": "archive", "datestamp": "2023-08-19 05:20:52", "lastmod": "2023-10-19 14:51:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kielkopf-C-L", "name": { "family": "Kielkopf", "given": "Clara L." } }, { "id": "Erkkila-K-E", "name": { "family": "Erkkila", "given": "Kathryn E." } }, { "id": "Hudson-B-P", "name": { "family": "Hudson", "given": "Brian P." } }, { "id": "Barton-J-K", "name": { "family": "Barton", "given": "Jacqueline K." }, "orcid": "0000-0001-9883-1600" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of a photoactive rhodium complex intercalated into DNA", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2000 Nature America Inc.\n\nReceived 30 September, 1999; accepted 17 December, 1999.\n\nWe are grateful to the NIH for research support and to the NSF and NIH for\npredoctoral fellowships to C.L.K and K.E.E. We thank L. Joshua-Tor, S.S. David,\nJ.E. Wedekind, A.J. Chirino and R. Bau for assistance with the structure solution,\nand S. Horvath for oligonucleotide synthesis. The rotation camera facility at SSRL\nis supported by the U.S. Department of Energy and NIH.", "abstract": "Intercalating complexes of rhodium(III) are strong photo-oxidants\nthat promote DNA strand cleavage or electron transfer\nthrough the double helix. The 1.2 \u00c5 resolution crystal structure\nof a sequence-specific rhodium intercalator bound to a DNA\nhelix provides a rationale for the sequence specificity of rhodium\nintercalators. It also explains how intercalation in the center\nof an oligonucleotide modifies DNA conformation. The\nrhodium complex intercalates via the major groove where specific\ncontacts are formed with the edges of the bases at the target\nsite. The phi ligand is deeply inserted into the DNA base pair\nstack. The primary conformational change of the DNA is a doubling\nof the rise per residue, with no change in sugar pucker\nfrom B-form DNA. Based upon the five crystallographically\nindependent views of an intercalated DNA helix observed in\nthis structure, the intercalator may be considered as an additional\nbase pair with specific functional groups positioned in\nthe major groove.", "date": "2000-02", "date_type": "published", "publication": "Nature Structural Biology", "volume": "7", "number": "2", "publisher": "Nature Publishing Group", "pagerange": "117-121", "id_number": "CaltechAUTHORS:20150108-155222366", "issn": "1072-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-155222366", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1038/72385", "resource_type": "article", "pub_year": "2000", "author_list": "Kielkopf, Clara L.; Erkkila, Kathryn E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sfqjw-kjn66", "eprint_id": 53419, "eprint_status": "archive", "datestamp": "2023-08-21 20:52:14", "lastmod": "2023-10-19 14:51:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kielkopf-C-L", "name": { "family": "Kielkopf", "given": "Clara L." } }, { "id": "Bremer-R-M", "name": { "family": "Bremer", "given": "Ryan M." } }, { "id": "White-S", "name": { "family": "White", "given": "Sarah" } }, { "id": "Szewczyk-J-W", "name": { "family": "Szewczyk", "given": "Jason W." } }, { "id": "Turner-J-M", "name": { "family": "Turner", "given": "James M." } }, { "id": "Baird-E-E", "name": { "family": "Baird", "given": "Eldon E." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural Effects of DNA Sequence on T\u2022A Recognition by Hydroxypyrrole/Pyrrole Pairs in the Minor Groove", "ispublished": "pub", "full_text_status": "restricted", "keywords": "polyamides; hydroxypyrrole; sequence-specific recognition; nucleic acids; crystal-structure", "note": "\u00a9 2000 Academic Press.\n\nReceived 1 September 1999; received in revised form 30 October 1999; accepted 2 November 1999.\n\nWe are grateful to the NIH for research support,\nto the NSF and NIH for predoctoral fellowships to\nC.L.K. and R.E.B., to J. Edward Richter for an undergraduate\nfellowship to J.M.T., and to the HHMI for a\npredoctoral fellowship to E.E.B. We thank A. Chirino\nand M. Williamson for assistance with computational\nand X-ray equipment, respectively, and S. Horvath for\noligonucleotide synthesis.", "abstract": "Synthetic polyamides composed of three types of aromatic amino acids, N-methylimidazole (Im), N-methylpyrrole (Py) and N-methyl-3-hydroxypyrrole (Hp) bind specific DNA sequences as antiparallel dimers in the minor groove. The side-by-side pairings of aromatic rings in the dimer afford a general recognition code that allows all four base-pairs to be distinguished. To examine the structural consequences of changing the DNA sequence context on T\u2022A recognition by Hp/Py pairs in the minor groove, crystal structures of polyamide dimers (ImPyHpPy)_2 and the pyrrole counterpart (ImPyPyPy)_2 bound to the six base-pair target site 5\u2032-AGATCT-3\u2032 in a ten base-pair oligonucleotide have been determined to a resolution of 2.27 and 2.15 \u00c5, respectively. The structures demonstrate that the principles of Hp/Py recognition of T\u2022A are consistent between different sequence contexts. However, a general structural explanation for the non-additive reduction in binding affinity due to introduction of the hydroxyl group is less clear. Comparison with other polyamide-DNA cocrystal structures reveals structural themes and differences that may relate to sequence preference.", "date": "2000-01-21", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "295", "number": "3", "publisher": "Elsevier", "pagerange": "557-567", "id_number": "CaltechAUTHORS:20150108-155336917", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-155336917", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1006/jmbi.1999.3364", "resource_type": "article", "pub_year": "2000", "author_list": "Kielkopf, Clara L.; Bremer, Ryan M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/bft58-he420", "eprint_id": 12022, "eprint_status": "archive", "datestamp": "2023-08-21 20:51:05", "lastmod": "2023-10-17 16:28:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Chang-G", "name": { "family": "Chang", "given": "Geoffrey" } }, { "id": "Spencer-R-H", "name": { "family": "Spencer", "given": "Robert H." } } ] }, "title": "Crystallographic Analyses of Ion Channels: Lessons and Challenges", "ispublished": "pub", "full_text_status": "public", "note": "Copyright \u00a9 2000 by the American Society for Biochemistry and Molecular Biology. \n\nThe contributions of A. Lee and M. Barclay to the MscL structural work and discussions with R. Bass, K. Locher, D. Dougherty, and H. Lester on channels and membrane proteins are greatly appreciated. \n\nThis minireview will be reprinted in the 2000 Minireview Compendium, which will be available in December, 2000.\n\nPublished - REEjbc00.pdf
", "abstract": "Membrane proteins fascinate at many levels, from their central functional roles in transport, energy transduction, and signal transduction processes to structural questions concerning how they fold and operate in the exotic environments of the membrane bilayer and the water-bilayer interface and to methodological issues associated with studying membrane proteins either in situ or extracted from the membrane. This interplay is beautifully exemplified by ion channels, a collection of integral membrane proteins that mediate the transmembrane passage of ions down their electrochemical potential gradient (for general reviews, see Refs. 1 and 2). Ion channels are key elements of signaling and sensing pathways, including nerve cell conduction, hormone response, and mechanosensation. The characteristic properties of ion channels reflect their conductance, ion selectivity, and gating. Ion channels are often specific for a particular type of ion (such as potassium or chloride) or a class of ions (such as anions) and are typically regulated by conformational switching of the protein structure between \"open\" and \"closed\" states. This conformational switching may be gated in response to changes in membrane potential, ligand binding, or application of mechanical forces. Detailed functional characterizations of channels and their gating mechanisms have been achieved, reflecting exquisite methodological advances such as patch clamp methods that can monitor the activities of individual channels (3). Until recently, corresponding information about the three-dimensional structures of channels was not available, reflecting difficulties in obtaining sufficient quantities of membrane proteins for crystallization trials. Happily, this situation has started to change with the structure determinations of the Streptomyces lividans K+ channel (KcsA (4)) and the Mycobacterium tuberculosis mechanosensitive channel (MscL (5)). \n\nA variety of reviews (6-12) have appeared recently that discuss functional implications of these channel structures. This review discusses these developments from a complementary perspective, by considering the implications of these structures from within the larger framework of membrane protein structure and function. Because of space restrictions, this review necessarily emphasizes membrane proteins that are composed primarily of alpha-helical bundles, such as KcsA and MscL, rather than beta-barrel proteins, such as porins, typically found in bacterial outer membranes.", "date": "2000-01-14", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "275", "number": "2", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "713-716", "id_number": "CaltechAUTHORS:REEjbc00", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:REEjbc00", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute" } ] }, "primary_object": { "basename": "REEjbc00.pdf", "url": "https://authors.library.caltech.edu/records/bft58-he420/files/REEjbc00.pdf" }, "resource_type": "article", "pub_year": "2000", "author_list": "Rees, Douglas C.; Chang, Geoffrey; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/trak2-47q24", "eprint_id": 53421, "eprint_status": "archive", "datestamp": "2023-08-22 14:05:53", "lastmod": "2023-10-19 14:51:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } } ] }, "title": "Structural Bioenergetics and Energy Transduction Mechanisms", "ispublished": "pub", "full_text_status": "restricted", "keywords": "biological energy transduction; nucleotide switch proteins; G-proteins; nitrogenase", "note": "\u00a9 1999 Academic Press.\n\n\n\nWe thank group members and collaborators for discussions\nand their contributions to the nitrogenase work\nfrom the authors' labs. This work was supported in part\nby NIH grant GM45162.", "abstract": "Life depends on transduction processes that couple cellular metabolism to environmental energy sources such as light or reduced compounds. These primary energy sources must be efficiently converted into forms that can be utilized by cells for biosynthesis, motility, transport, regulation, and other metabolic functions. In recent years, there has been an explosive increase in the determination of structures for proteins mediating energy transduction processes. These developments provide the opportunity to evaluate the structural basis for the efficient coupling of two energetic processes, which defines the area of structural bioenergetics. Here, we present some general features of energy transduction processes, including arguments that effective coupling of two processes by a transduction protein occurs by way of conformational states that are common to the catalysis of each process. This is illustrated by examples from the nucleotide switch family of proteins, with emphasis on the nitrogenase system where ATP hydrolysis is coupled to an electron transfer reaction.", "date": "1999-10-22", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "293", "number": "2", "publisher": "Elsevier", "pagerange": "343-350", "id_number": "CaltechAUTHORS:20150108-155622819", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-155622819", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1006/jmbi.1999.3005", "resource_type": "article", "pub_year": "1999", "author_list": "Rees, Douglas C. and Howard, James B." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n8epj-2jq90", "eprint_id": 53422, "eprint_status": "archive", "datestamp": "2023-08-19 04:34:31", "lastmod": "2023-10-20 23:29:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Spencer-R-H", "name": { "family": "Spencer", "given": "Robert H." } }, { "id": "Chang-G", "name": { "family": "Chang", "given": "Geoffrey" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Feeling the Pressure: Structural Insights into a Gated Mechanosensitive Channel", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1999 Published by Elsevier Ltd.\n\nThe contributions of AT Lee and MT Barclay to the Tb-MscL structural studies arc greatly appreciated. RHS and GC contributed equally to this work.", "abstract": "The structure determination of the large-conductance mechanosensitive channel (MscL) from Mycobacterium tuberculosis has revealed the architecture of the first full-length, gated pentameric ion channel. This structure provides insights into the elements participating in the conductance and gating mechanisms of these channels.", "date": "1999-08", "date_type": "published", "publication": "Current Opinion in Structural Biology", "volume": "9", "number": "4", "publisher": "Elsevier", "pagerange": "448-454", "id_number": "CaltechAUTHORS:20150108-155745445", "issn": "0959-440X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-155745445", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/S0959-440X(99)80063-3", "resource_type": "article", "pub_year": "1999", "author_list": "Spencer, Robert H.; Chang, Geoffrey; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qy3z4-ma250", "eprint_id": 52089, "eprint_status": "archive", "datestamp": "2023-08-19 04:28:12", "lastmod": "2023-10-18 19:33:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Luna-Chavez-C", "name": { "family": "Luna-Chavez", "given": "C\u00e9sar" } }, { "id": "Cecchini-G", "name": { "family": "Cecchini", "given": "Gary" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of the Escherichia coli Fumarate Reductase Respiratory Complex", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1999 American Association for the Advancement of Science.\n\nReceived 3 May 1999; accepted 21 May 1999.\n\nSupported by the Department of Veterans Affairs,\nNIH, and NSF (G.C. and C.L-C.), and the Howard\nHughes Medical Institute and NIH (D.C.R.). T.M.I. is\nsupported by an NIH training grant. We thank I.\nSchr\u00f6der, S. I. Chan, S. C. Hung, and the members\nof the Rees group for discussions; K. H. Tubman\nand T. D. Tubman for critical reading; and J. J.\nOttesen and T. N. Earnest for experimental assistance.\nThe Advanced Light Source is supported by\nthe Director, Office of Energy Research, Office of\nBasic Energy Sciences, Materials Sciences Division,\nof the U.S. Department of Energy under Contract\nNo. DE-AC03-76SF00098 at Lawrence Berkeley\nNational Laboratory.", "abstract": "The integral membrane protein fumarate reductase catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. The homologous enzyme succinate dehydrogenase also plays a prominent role in cellular energetics as a member of the Krebs cycle and as complex II of the aerobic respiratory chain. Fumarate reductase consists of four subunits that contain a covalently linked flavin adenine dinucleotide, three different iron-sulfur clusters, and at least two quinones. The crystal structure of intact fumarate reductase has been solved at 3.3 angstrom resolution and demonstrates that the cofactors are arranged in a nearly linear manner from the membrane-bound quinone to the active site flavin. Although fumarate reductase is not associated with any proton-pumping function, the two quinones are positioned on opposite sides of the membrane in an arrangement similar to that of the Q-cycle organization observed for cytochrome bc_1.", "date": "1999-06-18", "date_type": "published", "publication": "Science", "volume": "284", "number": "5422", "publisher": "American Association for the Advancement of Science", "pagerange": "1961-1966", "id_number": "CaltechAUTHORS:20141124-093703983", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141124-093703983", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Veterans Affairs" }, { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC03-76SF00098" } ] }, "doi": "10.1126/science.284.5422.1961", "resource_type": "article", "pub_year": "1999", "author_list": "Iverson, Tina M.; Luna-Chavez, C\u00e9sar; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sn6h3-sca03", "eprint_id": 53423, "eprint_status": "archive", "datestamp": "2023-08-22 13:41:22", "lastmod": "2023-10-19 14:51:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Grossmann-J-G", "name": { "family": "Grossmann", "given": "J. G\u00fcnter" } }, { "id": "Hasnain-S-S", "name": { "family": "Hasnain", "given": "S. Samar" } }, { "id": "Yousafzai-F-K", "name": { "family": "Yousafzai", "given": "Faridoon K." } }, { "id": "Smith-B-E", "name": { "family": "Smith", "given": "Barry E." } }, { "id": "Eady-R-R", "name": { "family": "Eady", "given": "Robert R." } }, { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Tsuruta-Hirotsugu", "name": { "family": "Tsuruta", "given": "Hirotsugu" } }, { "id": "Muller-J", "name": { "family": "Muller", "given": "Jurgen" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Comparing Crystallographic and Solution Structures of Nitrogenase Complexes", "ispublished": "pub", "full_text_status": "public", "keywords": "small-angle X-ray scattering; protein-protein interactions; nitrogenase complexes", "note": "\u00a9 1999 International Union of Crystallography.\n\nThe work was supported by the EPSRC/BBSRC Biomolecular Science grant\nGR/J54512 and by a grant from the NIH.\nThe small-angle scattering facility at SSRL is\nsupported by DOE and NIH. We are also\ngrateful for the provision of facilities at\nCCLRC Daresbury Laboratory and to Dr\nLoretta Murphy for her help and interest.\nWe acknowledge helpful comments from the\nreferees.\n\nPublished - 114_grossman_1999.pdf
", "abstract": "A low-resolution structure from X-ray scattering data of Kp1\u2022(ADP\u2022AlF-_4\u2022Kp2)2 predicted a significant change in the iron protein (Kp2) upon complex formation. This has been subsequently confirmed by the crystallographic structure of the complex in the Av system. New scattering results are provided to demonstrate the similarity of this complex in the two species.", "date": "1999-04", "date_type": "published", "publication": "Acta Crystallographica Section D: Biological Crystallography", "volume": "55", "number": "4", "publisher": "International Union of Crystallography", "pagerange": "727-728", "id_number": "CaltechAUTHORS:20150108-155917509", "issn": "0907-4449", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-155917509", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Engineering and Physical Sciences Research Council (EPSRC)", "grant_number": "GR/J54512" }, { "agency": "Biotechnology and Biological Sciences Research Council (BBSRC)" }, { "agency": "NIH" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1107/S0907444999003856", "primary_object": { "basename": "114_grossman_1999.pdf", "url": "https://authors.library.caltech.edu/records/sn6h3-sca03/files/114_grossman_1999.pdf" }, "resource_type": "article", "pub_year": "1999", "author_list": "Grossmann, J. G\u00fcnter; Hasnain, S. Samar; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f5bmp-5bn33", "eprint_id": 53424, "eprint_status": "archive", "datestamp": "2023-08-22 13:35:11", "lastmod": "2023-10-19 14:52:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hu-Yonglin", "name": { "family": "Hu", "given": "Yonglin" } }, { "id": "Faham-S", "name": { "family": "Faham", "given": "Salem" } }, { "id": "Roy-R", "name": { "family": "Roy", "given": "Roopali" } }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Formaldehyde Ferredoxin Oxidoreductase from Pyrococcus furiosus: The 1.85 \u00c5 Resolution Crystal Structure and its Mechanistic Implications", "ispublished": "pub", "full_text_status": "restricted", "keywords": "metalloenzymes; protein structure; tungstoenzyme; pterin; molybdenum cofactor", "note": "\u00a9 1999 Academic Press.\n\nReceived 14 September 1998; received in revised form 12 December 1998; accepted 12 December 1998.\n\nWe thank Dr Michael H. B. Stowell and Dr John W.\nPeters for assistance with data collection. This project is\nsupported by USPHS grants GM50775 (D.C.R.) and\nGM45587 (M.W.W.A.) and by the US Department of\nEnergy grant FG05-95ER20175 (M.W.W.A.). The rotation\ncamera facility at SSRL is supported by DOE and NIH.", "abstract": "Crystal structures of formaldehyde ferredoxin oxidoreductase (FOR), a tungstopterin-containing protein from the hyperthermophilic archaeon Pyrococcus furiosus, have been determined in the native state and as a complex with the inhibitor glutarate at 1.85 \u00c5 and 2.4 \u00c5 resolution, respectively. The native structure was solved by molecular replacement using the structure of the homologous P. furiosus aldehyde ferredoxin oxidoreductase (AOR) as the initial model. Residues are identified in FOR that may be involved in either the catalytic mechanism or in determining substrate specificity. The binding site on FOR for the physiological electron acceptor, P. furiosus ferredoxin (Fd), has been established from an FOR-Fd cocrystal structure. Based on the arrangement of redox centers in this structure, an electron transfer pathway is proposed that begins at the tungsten center, leads to the (4Fe:4S) cluster of FOR via one of the two pterins that coordinate the tungsten, and ends at the (4Fe:4S) cluster of ferredoxin. This pathway includes two residues that coordinate the (4Fe:4S) clusters, Cys287 of FOR and Asp14 of ferredoxin. Similarities in the active site structures between FOR and the unrelated molybdoenzyme aldehyde oxidoreductase from Desulfovibrio gigas suggest that both enzymes utilize a common mechanism for aldehyde oxidation.", "date": "1999-02-26", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "286", "number": "3", "publisher": "Elsevier", "pagerange": "899-914", "id_number": "CaltechAUTHORS:20150108-160056515", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160056515", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "USPHS", "grant_number": "GM50775" }, { "agency": "USPHS", "grant_number": "GM45587" }, { "agency": "Department of Energy (DOE)", "grant_number": "FG05-95ER20175" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH" } ] }, "doi": "10.1006/jmbi.1998.2488", "resource_type": "article", "pub_year": "1999", "author_list": "Hu, Yonglin; Faham, Salem; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r5are-71g83", "eprint_id": 53427, "eprint_status": "archive", "datestamp": "2023-08-19 03:58:22", "lastmod": "2023-10-19 14:52:16", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Faham-S", "name": { "family": "Faham", "given": "Salem" } }, { "id": "Day-M-W", "name": { "family": "Day", "given": "Michael W." } }, { "id": "Connick-W-B", "name": { "family": "Connick", "given": "William B." } }, { "id": "Crane-B-R", "name": { "family": "Crane", "given": "Brian R." } }, { "id": "Di-Bilio-A-J", "name": { "family": "Di Bilio", "given": "Angel J." } }, { "id": "Schaefer-W-P", "name": { "family": "Schaefer", "given": "William P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Gray-H-B", "name": { "family": "Gray", "given": "Harry B." }, "orcid": "0000-0002-7937-7876" } ] }, "title": "Structures of Ruthenium-modified Pseudomonas aeruginosa Azurin and [Ru(2,2'-bipyridine)_2(imidazole)_2)]SO_4\u202210H_2O", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1999 International Union of Crystallography.\n\nReceived 29 January 1998;\nAccepted 27 July 1998.\n\nWe thank Michael Harrington, Jack Mizoguchi, Larry\nHenling and Jack Richards for helpful discussions. This work\nwas supported by NIH (DK19038 to HBG; GM45162 to\nDCR).\n\nPublished - 108_faham_1998.pdf
", "abstract": "The crystal structure of Ru(2,2'-bipyridine)_2(imidazole)(His83)azurin (RuAz) has been determined to 2.3 \u00c5 \u00acresolution by X-ray crystallography. The spectroscopic and thermodynamic properties of both the native protein and [Ru(2,2'-bipyridine)_2(imidazole)_2]^(2+) are maintained in the modified protein. Dark-green RuAz crystals grown from PEG 4000, LiNO_3, CuCl_2 and Tris buffer are monoclinic, belong to the space group C2 and have cell parameters a = 100.6, b = 35.4, c = 74.7 \u00c5 and \u03b2 = 106.5\u00b0. In addition, [Ru(2,2'-bipyridine)_2(imidazole)_2]SO_4\u202210H_2O was synthesized, crystallized and structurally characterized by X-ray crystallography. Red-brown crystals of this complex are monoclinic, space group P2_1/n, unit-cell parameters a = 13.230 (2), b = 18.197 (4), c = 16.126 (4) \u00c5, \u03b2 = 108.65 (2)\u00b0. Stereochemical parameters for the refinement of Ru(2,2'-bipyridine)_2(imidazole)(His83) were taken from the atomic coordinates of [Ru(2,2'-bipyridine)_2(imidazole)_2]^(2+). The structure of RuAz confirms that His83 is the only site of chemical modification and that the native azurin structure is not perturbed significantly by the ruthenium label.", "date": "1999-02", "date_type": "published", "publication": "Acta Crystallographica Section D: Biological Crystallography", "volume": "55", "number": "2", "publisher": "International Union of Crystallography", "pagerange": "379-385", "id_number": "CaltechAUTHORS:20150108-160523362", "issn": "0907-4449", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160523362", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "DK19038" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1107/S0907444998010464", "primary_object": { "basename": "108_faham_1998.pdf", "url": "https://authors.library.caltech.edu/records/r5are-71g83/files/108_faham_1998.pdf" }, "resource_type": "article", "pub_year": "1999", "author_list": "Faham, Salem; Day, Michael W.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/svvch-2e550", "eprint_id": 52182, "eprint_status": "archive", "datestamp": "2023-08-19 03:39:09", "lastmod": "2023-10-18 19:38:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chang-Geoffrey", "name": { "family": "Chang", "given": "Geoffrey" } }, { "id": "Spencer-R-H", "name": { "family": "Spencer", "given": "Robert H." } }, { "id": "Lee-Allen-T", "name": { "family": "Lee", "given": "Allen T." } }, { "id": "Barclay-Margaret-T", "name": { "family": "Barclay", "given": "Margaret T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of the MscL Homolog from Mycobacterium tuberculosis: A Gated Mechanosensitive Ion Channel", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1998 American Association for the Advancement of Science.\n\n29 October 1998; Accepted 16 November 1998.\n\nWe thank A. Chirino for advice and computer support, J. G. Spencer for technical assistance, S. Gordon of the Institut Pasteur (Paris, France) for his kind gift of genomic DNA from M. tuberculosis, C. Kung and P. C. Moe from the University of Wisconsin-Madison for several cloned mscL homologs and for the E. coli knockout mutant for mscL, A. Okabe of the Kagawa Medical School (Kagawa, Japan) for providing cloned DNA of mscL from C. perfringens, and D. Dougherty and H. Lester for helpful discussions. We also thank the staff at the Stanford Synchrotron Radiation Laboratory (SSRL) and the Advanced Light Source (ALS) for their help in data collection. The synchrotron rotation camera facilities are supported by the U.S. Department of Energy (ALS and SSRL) and NIH (SSRL). G.C. and R.H.S. were\nsupported by NIH postdoctoral fellowship grant GM18486 and an Amgen postdoctoral fellowship, respectively, during the initial stages of this project. Supported by the Howard Hughes Medical Institute. Protein Data Bank identifier for Tb-MscL is 1MSL.", "abstract": "Mechanosensitive ion channels play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. The MscL family of large-conductance mechanosensitive channels is widely distributed among prokaryotes and may participate in the regulation of osmotic pressure changes within the cell. In an effort to better understand the structural basis for the function of these channels, the structure of the MscL homolog fromMycobacterium tuberculosis was determined by x-ray crystallography to 3.5 angstroms resolution. This channel is organized as a homopentamer, with each subunit containing two transmembrane \u03b1 helices and a third cytoplasmic \u03b1 helix. From the extracellular side, a water-filled opening approximately 18 angstroms in diameter leads into a pore lined with hydrophilic residues which narrows at the cytoplasmic side to an occluded hydrophobic apex that may act as the channel gate. This structure may serve as a model for other mechanosensitive channels, as well as the broader class of pentameric ligand-gated ion channels exemplified by the nicotinic acetylcholine receptor.", "date": "1998-12-18", "date_type": "published", "publication": "Science", "volume": "282", "number": "5397", "publisher": "American Association for the Advancement of Science", "pagerange": "2220-2226", "id_number": "CaltechAUTHORS:20141126-121449196", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141126-121449196", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NIH", "grant_number": "GM18486" }, { "agency": "Amgen" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1126/science.282.5397.2220", "resource_type": "article", "pub_year": "1998", "author_list": "Chang, Geoffrey; Spencer, Robert H.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hqgz6-97479", "eprint_id": 53425, "eprint_status": "archive", "datestamp": "2023-08-19 03:28:30", "lastmod": "2023-10-19 14:52:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-T-M", "name": { "family": "Iverson", "given": "Tina M." } }, { "id": "Arciero-D-M", "name": { "family": "Arciero", "given": "David M." } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "Barbara T." } }, { "id": "Logan-M-S-P", "name": { "family": "Logan", "given": "Michael S .P." } }, { "id": "Hooper-A-B", "name": { "family": "Hooper", "given": "Alan B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Heme Packing Motifs Revealed by the Crystal Structure of the Tetra-heme Cytochrome c554 from Nitrosomonas europaea", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1998 Nature America Inc.\n\nReceived 26 June, 1998; accepted 14 September, 1998.\n\nWe thank J. Hu, L. Joshua-Tor, M. Stowell, D. Cascio, M. Soltis, H. Schindelin,\nC. Kisker and C. Kielkopf for experimental assistance; C. Drennan and H.\nAxelrod for critical reading and helpful discussions; K. Matthews and B. Crane\nfor the microspectrophotometery; M. Carrondo for the split Soret cytochrome\ncoordinates; and R. Timkovich for the cytochrome c552 coordinates. This work\nwas supported by an NSF grant to A.B.H and an NIH grant to D.C.R. T.M.I. is\nsupported by an NIH fellowship. The rotation camera facility at SSRL is\nsupported by the NIH and Department of Energy.", "abstract": "Cytochrome c554 (cyt c554), a tetra-heme cytochrome from Nitrosomonas europaea, is an essential component in the biological nitrification pathway. In N. europaea, ammonia is converted to hydroxylamine, which is then oxidized to nitrite by hydroxylamine oxidoreductase (HAO). Cyt c554 functions in the latter process by accepting pairs of electrons from HAO and transferring them to a cytochrome acceptor. The crystal structure of cyt c554 at 2.6 \u00c5 resolution shows a predominantly alpha-helical protein with four covalently attached hemes. The four hemes are arranged in two pairs such that the planes of the porphyrin rings are almost parallel and overlapping at the edge; corresponding heme arrangements are observed in other multi-heme proteins. Striking structural similarities are evident between the tetra-heme core of cyt c554 and hemes 3\u22126 of HAO, which suggests an evolutionary relationship between these redox partners.", "date": "1998-11", "date_type": "published", "publication": "Nature Structural Biology", "volume": "5", "number": "11", "publisher": "Nature Publishing Group", "pagerange": "1005-1012", "id_number": "CaltechAUTHORS:20150108-160218407", "issn": "1072-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160218407", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF" }, { "agency": "NIH" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1038/2975", "resource_type": "article", "pub_year": "1998", "author_list": "Iverson, Tina M.; Arciero, David M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/a23j8-0hh31", "eprint_id": 52137, "eprint_status": "archive", "datestamp": "2023-08-19 03:24:28", "lastmod": "2023-10-18 19:36:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kielkopf-C-L", "name": { "family": "Kielkopf", "given": "Clara L." } }, { "id": "White-S", "name": { "family": "White", "given": "Sarah" } }, { "id": "Szewczyk-J-W", "name": { "family": "Szewczyk", "given": "Jason W." } }, { "id": "Turner-J-M", "name": { "family": "Turner", "given": "James M." } }, { "id": "Baird-E-E", "name": { "family": "Baird", "given": "Eldon E." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A Structural Basis for Recognition of A\u00b7T and T\u00b7A Base Pairs in the Minor Groove of B-DNA", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1998 American Association for the Advancement of Science.\n\nReceived 26 June 1998; accepted 25 August 1998.\n\nWe are grateful to the NIH for research support, to\nthe NSF for a predoctoral fellowship to C.L.K., to J.\nEdward Richter for an undergraduate fellowship to\nJ.M.T., and to the Howard Hughes Medical Institute\nfor a predoctoral fellowship to E.E.B. We thank J. E.\nWedekind, C. L. Drennan, T. M. Iverson, and M. Williamson\nfor assistance with data collection and S.\nHorvath for oligonucleotide synthesis. The rotation\ncamera facility at SSRL is supported by the U.S.\nDepartment of Energy and NIH. Coordinates have\nbeen deposited in the Nucleic Acid Database with\naccession numbers BDD002 (ImHpPyPy) and BDD003\n(ImPyPyPy).", "abstract": "Polyamide dimers containing three types of aromatic rings\u2014pyrrole, imidazole, and hydroxypyrrole\u2014afford a small-molecule recognition code that discriminates among all four Watson-Crick base pairs in the minor groove. The crystal structure of a specific polyamide dimer-DNA complex establishes the structural basis for distinguishing T\u00b7A from A\u00b7T base pairs. Specificity for the T\u00b7A base pair is achieved by means of distinct hydrogen bonds between pairs of substituted pyrroles on the ligand and the O2 of thymine and N3 of adenine. In addition, shape-selective recognition of an asymmetric cleft between the thymine-O2 and the adenine-C2 was observed. Although hitherto similarities among the base pairs in the minor groove have been emphasized, the structure illustrates differences that allow specific minor groove recognition.", "date": "1998-10-02", "date_type": "published", "publication": "Science", "volume": "282", "number": "5386", "publisher": "American Association for the Advancement of Science", "pagerange": "111-115", "id_number": "CaltechAUTHORS:20141125-100839997", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141125-100839997", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF Predoctoral Fellowship" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1126/science.282.5386.111", "resource_type": "article", "pub_year": "1998", "author_list": "Kielkopf, Clara L.; White, Sarah; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xp0hs-6vn77", "eprint_id": 53429, "eprint_status": "archive", "datestamp": "2023-08-22 13:10:08", "lastmod": "2023-10-19 14:52:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bau-R", "name": { "family": "Bau", "given": "Robert" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Kurtz-D-M-Jr", "name": { "family": "Kurtz", "given": "Donald M., Jr." } }, { "id": "Scott-R-A", "name": { "family": "Scott", "given": "Robert A." } }, { "id": "Huang-Heshu", "name": { "family": "Huang", "given": "Heshu" } }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Eidsness-M-K", "name": { "family": "Eidsness", "given": "Marly K." } } ] }, "title": "Crystal structure of rubredoxin from Pyrococcus furiosus at 0.95\u2009\u00c5 resolution, and the structures of N-terminal methionine and formylmethionine variants of Pf Rd. Contributions of N-terminal interactions to thermostability", "ispublished": "pub", "full_text_status": "restricted", "keywords": "rubredoxin; iron-sulfur proteins; hyperthermostability; protein structure; metalloproteins", "note": "\u00a9 1998 SBIC. \n\nReceived: 27 March 1998; Accepted: 25 June 1998. \n\nThis work was supported by the National Science Foundation (Grant DMB 91-18689 to D.C.R., Grant BCS-96-32657 to M.W.W.A.), the National Institutes of Health (Grant GM-50736 to D.M.K.), and NSF Research Training Group Award DIR-90-14281 to the Center for Metalloenzyme Studies, University of Georgia. R.B. acknowledges sabbatical leave support from the University of Southern California.", "abstract": "The high-resolution crystal structure of the small iron-sulfur protein rubredoxin (Rd) from the hyperthermophilic archeon Pyrococcus furiosus (Pf) is reported in this paper, together with those of its methionine ([_0M]Pf Rd) and formylmethionine (f[_0M]Pf Rd) variants. These studies were conducted to assess the consequences of the presence or absence of a salt bridge between the amino terminal nitrogen of Ala1 and the side chain of Glu14 to the structure and stability of this rubredoxin. The structure of wild-type Pf Rd was solved to a resolution of 0.95\u2009\u00c5 and refined by full-matrix least-squares techniques to a crystallographic agreement factor of 12.8% [F>2\u03c3(F) data, 25\u2009617 reflections], while those of the [_0M]Pf and f[_0M]Pf Rd variants were solved at slightly lower resolutions (1.1\u2009\u00c5, R=11.5%, 17\u2009213 reflections; 1.2\u2009\u00c5, R=13.7%, 12\u2009478 reflections, respectively). The quality of the data was such that about half of the hydrogen atoms of the protein were clearly visible. All three structures were ultimately refined using the program SHELXL-93 with anisotropic atomic displacement parameters for all non-hydrogen protein atoms, and calculated hydrogen positions included but not refined. In this paper we also report thermostability data for all three forms of Pf Rd, and show that they follow the sequence wild-type >[_0M]Pf>formyl[_0M]Pf. Comparison of the three Pf Rd structures in the N-terminal region show that the structures of wild-type Pf Rd and f[_0M]Pf are rather similar, while that of [_0M]Pf Rd shows a number of additional hydrogen bonds involving the extra methionine group. While the salt bridge between the Ala1 amino group and the Glu14 carboxylate is not the primary determinant of the thermostability of Pf Rd, alterations to the amino terminus do have a moderate influence on the thermostability of this protein.", "date": "1998-10", "date_type": "published", "publication": "Journal of Biological Inorganic Chemistry", "volume": "3", "number": "5", "publisher": "Springer", "pagerange": "484-493", "id_number": "CaltechAUTHORS:20150108-160800902", "issn": "0949-8257", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160800902", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB 91-18689" }, { "agency": "NSF", "grant_number": "BCS-96-32657" }, { "agency": "NIH", "grant_number": "GM-50736" }, { "agency": "NSF", "grant_number": "DIR-90-14281" } ] }, "doi": "10.1007/s007750050258", "resource_type": "article", "pub_year": "1998", "author_list": "Bau, Robert; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/nvcx9-wy147", "eprint_id": 53426, "eprint_status": "archive", "datestamp": "2023-08-19 03:21:44", "lastmod": "2023-10-19 14:52:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Faham-S", "name": { "family": "Faham", "given": "Salem" } }, { "id": "Linhardt-R-J", "name": { "family": "Linhardt", "given": "Robert J." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Diversity Does Make a Difference: Fibroblast Growth Factor-Heparin Interactions", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1998 Current Biology Ltd.\n\n\n\nWe thank T Arakawa, JR Fromm, GM Fox, RE Hileman and D Bar-Shalom\nfor discussions of FGF and hepatic-related research conducted in the\nauthors' laboratories, and A DiGabriele and WA Hendrickson for providing\na preprint of their work on the FGF-l-heparin structure. SF was supported\nby the Alexander Hollaender Distinguished Postdoctoral Fellowship\nProgram, sponsored by the DOE-OHER. Support for RJL was from\nNational Institutes of Health grants GM38060 and HL52622.", "abstract": "Fibroblast growth factors (FGFs) are members of a protein family with a broad range of biological activities. The best characterized FGFs interact with two distinct extracellular receptors \u2014 a transmembrane tyrosine kinase FGF receptor (FGFR) and a heparan sulfate-related proteoglycan of the extracellular matrix. These components form a FGF\u2014FGFR\u2014proteoglycan complex that activates the FGF-mediated signal transduction process through FGFR dimerization. Recent crystal structure determinations of FGF\u2014heparin complexes have provided insights into both the interactions between these components and the role of heparin-like proteoglycans in FGF function. Future advances in this field will benefit enormously from an ability to specifically prepare homogenous heparin-based oligosaccharides of defined sequence for use in biochemical and structural studies of FGF and many other systems.", "date": "1998-10", "date_type": "published", "publication": "Current Opinion in Structural Biology", "volume": "8", "number": "5", "publisher": "Elsevier", "pagerange": "578-586", "id_number": "CaltechAUTHORS:20150108-160400458", "issn": "0959-440X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160400458", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM38060" }, { "agency": "NIH", "grant_number": "HL52622" }, { "agency": "Alexander Hollaender Distinguished Postdoctoral Fellowship" } ] }, "doi": "10.1016/S0959-440X(98)80147-4", "resource_type": "article", "pub_year": "1998", "author_list": "Faham, Salem; Linhardt, Robert J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/d8hmf-9rh63", "eprint_id": 53428, "eprint_status": "archive", "datestamp": "2023-08-22 13:01:13", "lastmod": "2023-10-19 14:52:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schlessman-J-L", "name": { "family": "Schlessman", "given": "James L." } }, { "id": "Woo-D", "name": { "family": "Woo", "given": "Deborah" } }, { "id": "Joshua-Tor-L", "name": { "family": "Joshua-Tor", "given": "Leemor" } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Conformational Variability in Structures of the Nitrogenase Iron Proteins from Azotobacter vinelandii and Clostridium pasteurianum", "ispublished": "pub", "full_text_status": "restricted", "keywords": "nitrogen fixation; nucleotide-binding proteins; iron-sulfur proteins; metalloproteins; macromolecular structure", "note": "\u00a9 1998 Academic Press.\n\nReceived 2 March 1998; received in revised form 20 April 1998; accepted 22 April 1998.\n\nThis work was supported by USPHS grant GM45162.\nThe advice and contributions of A. J. Chirino, M. M.\nGeorgiadis, B. T. Hsu, C. Kisker, C. L. Kielkopf,\nH. Komiya, J. J. Kornuc, J. W. Peters, H. Schindelin and\nM. H. B. Stowell to this project are gratefully appreciated,\nas is the support of D. S. Eisenberg and the UCLA\nstructural biology group during the early phases of this\nwork. The advice of R. Bare (Exxon) concerning the\nC. pasteurianum preparations was invaluable. The\nrotation camera facility at SSRL is supported by the DOE\nOffice of Basic Energy Sciences and the NIH Biomedical\nResearch Technology Program, Division of Research\nResources.", "abstract": "The nitrogenase iron (Fe) protein performs multiple functions during biological nitrogen fixation, including mediating the mechanistically essential coupling between ATP hydrolysis and electron transfer to the nitrogenase molybdenum iron (MoFe) protein during substrate reduction, and participating in the biosynthesis and insertion of the FeMo-cofactor into the MoFe-protein. To establish a structural framework for addressing the diverse functions of Fe-protein, crystal structures of the Fe-proteins from Azotobacter vinelandii and Clostridium pasteurianum have been determined at resolutions of 2.2 \u00c5 and 1.93 \u00c5, respectively. These two Fe-proteins are among the more diverse in terms of amino acid sequence and biochemical properties. As described initially for the A. vinelandii Fe-protein in a different crystal form at 2.9 \u00c5 resolution, each subunit of the dimeric Fe-protein adopts a polypeptide fold related to other mononucleotide-binding proteins such as G-proteins, with the two subunits bridged by a 4Fe:4S cluster. The overall similarities in the subunit fold and dimer arrangement observed in the structures of the A. vinelandii and C. pasteurianum Fe-proteins indicate that they are representative of the conformation of free Fe-protein that is not in complex with nucleotide or the MoFe-protein. Residues in the cluster and nucleotide-binding sites are linked by a network of conserved hydrogen bonds, salt-bridges and water molecules that may conformationally couple these regions. Significant variability is observed in localized regions, especially near the 4Fe:4S cluster and the MoFe-protein binding surface, that change conformation upon formation of the ADP\u2022AlF_4\u2212stabilized complex with the MoFe-protein. A core of 140 conserved residues is identified in an alignment of 59 Fe-protein sequences that may be useful for the identification of homologous proteins with functions comparable to that of Fe-protein in non-nitrogen fixing systems.", "date": "1998-07-24", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "280", "number": "4", "publisher": "Elsevier", "pagerange": "669-685", "id_number": "CaltechAUTHORS:20150108-160637954", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160637954", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "USPHS", "grant_number": "GM45162" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH Biomedical Research Technology Program" } ] }, "doi": "10.1006/jmbi.1998.1898", "resource_type": "article", "pub_year": "1998", "author_list": "Schlessman, James L.; Woo, Deborah; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1564t-jyz62", "eprint_id": 53430, "eprint_status": "archive", "datestamp": "2023-08-19 02:28:32", "lastmod": "2023-10-19 14:52:34", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kielkopf-C-L", "name": { "family": "Kielkopf", "given": "Clara L." } }, { "id": "Baird-E-E", "name": { "family": "Baird", "given": "Eldon E." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural Basis for G\u2022C Recognition in the DNA Minor Groove", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1998 Nature Publishing Group.\n\nReceived 3 November, 1997; accepted 30 December, 1997.\n\nWe are grateful to the NIH for research support, the NSF for a predoctoral fellowship\nto C.L.K., and the HHMI for a predoctoral fellowship to E.E.B. We thank JE.\nWedekind, H. Schindelin, C. Kisker, L. Joshua-Tor, PM. Takahara and the members of\nthe Rees group for guidance during the structure determination. The rotation camera\nfacility at SSRL is supported by the Department of Energy and NIH.", "abstract": "Small molecules that target specific DNA sequences offer a potentially general approach for the regulation of gene expression. Pyrrole\u2212imidazole polyamides represent the only class of synthetic small molecules that can bind predetermined DNA sequences with affinities and specificities comparable to DNA binding proteins. Antiparallel side-by-side pairings of two aromatic amino acids, imidazole (Im) and pyrrole (Py), distinguish G\u2022C from C\u2022G, and both from A\u2022T/T\u2022A base pairs. A high resolution X-ray crystal structure of a four-ring pyrrole\u2212imidazole polyamide specifically bound as a dimer to a six-base pair predetermined DNA site reveals a structural framework of hydrogen bonds and interactions with the walls of the minor groove that underlies the pairing rules for DNA recognition.", "date": "1998-02", "date_type": "published", "publication": "Nature Structural Biology", "volume": "5", "number": "2", "publisher": "Nature Publishing Group", "pagerange": "104-109", "id_number": "CaltechAUTHORS:20150108-160953214", "issn": "1072-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150108-160953214", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1038/nsb0298-104", "resource_type": "article", "pub_year": "1998", "author_list": "Kielkopf, Clara L.; Baird, Eldon E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k24mf-hh010", "eprint_id": 12028, "eprint_status": "archive", "datestamp": "2023-08-22 12:00:42", "lastmod": "2023-10-17 16:28:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Hu-Y", "name": { "family": "Hu", "given": "Yonglin" } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } } ] }, "title": "A crystallographic view of the molybdenum cofactor", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 Royal Society of Chemistry 1997. \n\nReceived 10th June 1997; Paper 7/04048B. \n\nWe thank group members and M.W.W. Adams, J.H. Enemark and K.V. Rajagopalan for stimulating discussions and collaborations. This work was supported by USPHS grant GM50775 and Deutsche Forschungsgemeinschaft postdoctoral fellowships\n(to C.K. and H.S.).\n\nBased on the presentation given at Dalton Discussion No. 2, 2nd\u20135th September 1997, University of East Anglia, UK.\n\nPublished - REEjcsdt97.pdf
", "abstract": "The molybdenum cofactor (Moco) has been found to be associated with a diverse set of redox enzymes and contains a mononuclear molybdenum or tungsten ion co-ordinated by the dithiolene sulfurs of one or two molybdopterin {a pterin [2-amino-4(1H)-pteridinone] derivative} ligands. The remaining co-ordination sites on the metal are occupied by non-protein oxygen or sulfur species and, occasionally, amino acid side chains. The molybdopterin ligand can exhibit oxidation-state-dependent changes in structure and metal co-ordination, and may also interact with other redox groups in the enzyme. These observations suggest that the molybdopterin may participate in the various electron-transfer reactions associated with the catalytic mechanism of Moco containing enzymes.", "date": "1997-11-07", "date_type": "published", "publication": "Journal of the Chemical Society. Dalton Transactions", "volume": "1997", "number": "21", "publisher": "Royal Society of Chemistry", "pagerange": "3909-3914", "id_number": "CaltechAUTHORS:REEjcsdt97", "issn": "0300-9246", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:REEjcsdt97", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Public Health Service", "grant_number": "GM50775" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)" } ] }, "doi": "10.1039/a704048b", "primary_object": { "basename": "REEjcsdt97.pdf", "url": "https://authors.library.caltech.edu/records/k24mf-hh010/files/REEjcsdt97.pdf" }, "resource_type": "article", "pub_year": "1997", "author_list": "Rees, Douglas C.; Hu, Yonglin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4acjm-agr41", "eprint_id": 54434, "eprint_status": "archive", "datestamp": "2023-08-19 01:48:09", "lastmod": "2023-10-20 16:27:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Magnuson-J-K", "name": { "family": "Magnuson", "given": "Jon K." } }, { "id": "Paustian-T-D", "name": { "family": "Paustian", "given": "Timothy D." } }, { "id": "Shah-V-K", "name": { "family": "Shah", "given": "Vinod K." } }, { "id": "Dean-D-R", "name": { "family": "Dean", "given": "Dennis R." } }, { "id": "Roberts-G-P", "name": { "family": "Roberts", "given": "Gary P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } } ] }, "title": "Nitrogenase Iron-Molybdenum Cofactor Binding Site: Protein Conformational Changes Associated with Cofactor Binding", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1997 Elsevier Science Ltd.\n\nReceived 10 April 1997; accepted 12 June 1997.\n\nThis work was supported by NSF grants MCB-9513512 (JBH), MCB-9317059 (GR), MCB-9630127 (DD) and DMB 91-18689.", "abstract": "Formation of active nitrogenase MoFe-protein requires the assembly and insertion of a unique molybdenum containing Fe:S cluster, the FeMoco. The protein acceptor is held in an open conformation by the binding of a small molecular weight protein, \u03b3. Using selective alkylation of the protein cysteines, conformational changes associated with \u03b3 binding and cofactor insertion were evaluated and a model for the change presented. Reversible oxygen damage to the precursor is identified and evaluated in terms of the chemistry of dithionite used in the buffer as an oxygen scavenger.", "date": "1997-09-01", "date_type": "published", "publication": "Tetrahedron", "volume": "53", "number": "35", "publisher": "Elsevier", "pagerange": "11971-11984", "id_number": "CaltechAUTHORS:20150205-140103112", "issn": "0040-4020", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140103112", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-9513512" }, { "agency": "NSF", "grant_number": "MCB-9317059" }, { "agency": "NSF", "grant_number": "MCB-9630127" }, { "agency": "NSF", "grant_number": "DMB 91-18689" } ] }, "collection": "CaltechAUTHORS", "doi": "10.1016/S0040-4020(97)00710-2", "resource_type": "article", "pub_year": "1997", "author_list": "Magnuson, Jon K.; Paustian, Timothy D.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/g4fcm-gb931", "eprint_id": 54432, "eprint_status": "archive", "datestamp": "2023-08-19 01:45:56", "lastmod": "2023-10-20 16:27:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hu-Yonglin", "name": { "family": "Hu", "given": "Yonglin" } }, { "id": "Rech-S", "name": { "family": "Rech", "given": "Sabina" } }, { "id": "Gunsalus-R-P", "name": { "family": "Gunsalus", "given": "Robert P." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structure of the Molybdate Binding Protein ModA", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1997 Nature Publishing Group.\n\nReceived 24April 1997; accepted 2 July 1997.\n\nThis work was supported by NIH grants to RPG and DCR.", "abstract": "The specificity exhibited by the molybdate binding protein ModA for molybdate and tungstate reflects the size and ligands of the anion binding pocket.", "date": "1997-09", "date_type": "published", "publication": "Nature Structural Biology", "volume": "4", "number": "9", "publisher": "Nature Publishing Group", "pagerange": "703-707", "id_number": "CaltechAUTHORS:20150205-135846197", "issn": "1072-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-135846197", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" } ] }, "doi": "10.1038/nsb0997-703", "resource_type": "article", "pub_year": "1997", "author_list": "Hu, Yonglin; Rech, Sabina; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p42b6-emy71", "eprint_id": 54431, "eprint_status": "archive", "datestamp": "2023-08-22 11:50:35", "lastmod": "2023-10-20 16:27:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Faham-S", "name": { "family": "Faham", "given": "Salem" } }, { "id": "Mizoguchi-T-J", "name": { "family": "Mizoguchi", "given": "Tadashi J." } }, { "id": "Adman-E-T", "name": { "family": "Adman", "given": "Elinor T." } }, { "id": "Gray-H-B", "name": { "family": "Gray", "given": "Harry B." }, "orcid": "0000-0002-7937-7876" }, { "id": "Richards-J-H", "name": { "family": "Richards", "given": "John H." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Role of the active-site cysteine of Pseudomonas aeruginosa azurin. Crystal structure analysis of the Cu^(II(Cys112Asp) protein", "ispublished": "pub", "full_text_status": "restricted", "keywords": "azurin; cytochrome c(551); electron transfer; site-directed mutagenesis; protein crystallography", "note": "\u00a9 1997 SBIC.\n\nReceived: 30 December 1996; Accepted: 8 May 1997.\n\nWe thank Mike Hill for assistance with several electrochemical experiments, and Xiaotian Zhu, Art Chirino and Barbara Hsu for their help with the crystallographic analysis. S.F. and T.J.M. contributed equally to this work; supported by the NIH (DK19038 to H.B.G., GM16424 to J.H.R., and GM45162 to D.C.R.).", "abstract": "Replacement of the cysteine at position 112 of Pseudomonas aeruginosa azurin with an aspartic acid residue results in a mutant (Cys112Asp) protein that retains a strong copper-binding site. Cu^(II)(Cys112Asp) azurin can be reduced by excess [Ru^(II)(NH_3)_6]^(2+), resulting in a Cu^I protein with an electronic absorption spectrum very similar to that of wild-type Cu^I azurin. Cys112Asp azurin exhibits reversible interprotein electron-transfer reactivity with P. aeruginosa cytochrome c_(551) (\u03bc\u2009=\u20090.1\u2009M sodium phosphate (pH\u20097.0);E\u00b0(Cu^(II/I))\u2009=\u2009180 mV vs NHE); this redox activity indicates that electrons can still enter and exit the protein through the partially solvent-exposed imidazole ring of His117. The structure of Cu^(II)(Cys112Asp) azurin at 2.4-\u00c5 resolution shows that the active-site copper is five coordinate: the pseudo-square base of the distorted square-pyramidal structure is defined by the imidazole N^\u03b4 atoms of His46 and His117 and the oxygen atoms of an asymmetrically-bound bidentate carboxylate group of Asp112; the apical position is occupied by the oxygen atom of the backbone carbonyl group of Gly45. The Cu^(II)\u2013Asp112 interaction is distinguished by an approximately 1.2-\u00c5 displacement of the metal center from the plane defined by the Asp112 carboxylate group.", "date": "1997-08", "date_type": "published", "publication": "Journal of Biological Inorganic Chemistry", "volume": "2", "number": "4", "publisher": "Springer", "pagerange": "464-469", "id_number": "CaltechAUTHORS:20150205-135731010", "issn": "0949-8257", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-135731010", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "DK19038" }, { "agency": "NIH", "grant_number": "GM16424" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1007/s007750050157", "resource_type": "article", "pub_year": "1997", "author_list": "Faham, Salem; Mizoguchi, Tadashi J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/erdjw-b1v13", "eprint_id": 630, "eprint_status": "archive", "datestamp": "2023-08-22 11:46:49", "lastmod": "2023-10-13 21:54:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Molybdenum-cofactor-containing enzymes: structure and mechanism", "ispublished": "pub", "full_text_status": "public", "keywords": "molybdopterin, molybdoenzymes, tungstoenzymes, oxotransferases, molybdenum hydroxylases", "note": "\u00a9 1997 by Annual Reviews Inc. \n\nSupported by Deutsche Forschungsgemeinschaft postdoctoral fellowships (to CK and HS) and by USPHS grant GM50775 (to DCR). The authors would like to thank group members and MWW Adams, J Enemark, J Hilton, MK Johnson, and KV Rajagopalan for stimulating discussions and collaborations on Mo-co-containing enzymes.\n\nPublished - KISarb97.pdf
", "abstract": "Molybdenum-containing enzymes catalyze basic metabolic reactions in the nitrogen, sulfur, and carbon cycles. With the exception of the nitrogenase cofactor, molybdenum is incorporated into proteins as the molybdenum cofactor that contains a mononuclear molybdenum atom coordinated to the sulfur atoms of a pterin derivative named molybdopterin. Certain microorganisms can also utilize tungsten in a similar fashion. Molybdenum-cofactor-containing enzymes catalyze the transfer of an oxygen atom, ultimately derived from or incorporated into water, to or from a substrate in a two-electron redox reaction. On the basis of sequence alignments and spectroscopic properties, four families of molybdenum-cofactor-containing enzymes have been identified. The available crystallographic structures for members of these families are discussed within the framework of the active site structure and catalytic mechanisms of molybdenum-cofactor-containing enzymes. Although the function of the molybdopterin ligand has not yet been conclusively established, interactions of this ligand with the coordinated metal are sensitive to the oxidation state, indicating that the molybdopterin may be directly involved in the enzymatic mechanism.", "date": "1997-07", "date_type": "published", "publication": "Annual Review of Biochemistry", "volume": "66", "publisher": "Annual Reviews", "pagerange": "233-267", "id_number": "CaltechAUTHORS:KISarb97", "issn": "0066-4154", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:KISarb97", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Deutsche Forschungsgemeinschaft (DFG)" }, { "agency": "NIH", "grant_number": "GM50775" } ] }, "doi": "10.1146/annurev.biochem.66.1.233", "primary_object": { "basename": "KISarb97.pdf", "url": "https://authors.library.caltech.edu/records/erdjw-b1v13/files/KISarb97.pdf" }, "resource_type": "article", "pub_year": "1997", "author_list": "Kisker, Caroline; Schindelin, Hermann; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xcn8b-x2p46", "eprint_id": 58326, "eprint_status": "archive", "datestamp": "2023-08-19 01:23:23", "lastmod": "2023-10-23 19:15:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Schlessman-J-L", "name": { "family": "Schlessman", "given": "Jamie L." } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of ADP\u00b7AIF_4 -stabilized nitrogenase complex and its implications for signal transduction", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1997 Nature Publishing Group. Received 5 December 1996; accepted 26 March 1997.\n\nSupported by the NIH (D.C.R. and J.B.H.), the NSF (J.B.H.) and by Deutsche Forschungsgemeinschaft postdoctoral fellowships (to C.K. and H.S.). X-PLOR calculations were performed on the CRAY C90 at the San Diego Supercomputer Center, supported by the NSF.", "abstract": "The coupling of ATP hydrolysis to electron transfer by the enzyme nitrogenase during biological nitrogen fixation is an important example of a nucleotide-dependent transduction mechanism. The crystal structure has been determined for the complex between the Fe-protein and MoFe-protein components of nitrogenase stabilized by ADP\u00b7AIF_4 \u2013, previously used as a nucleoside triphosphate analogue in nucleotide-switch proteins. The structure reveals that the dimeric Fe-protein has undergone substantial conformational changes. The \u03b2-phosphate and AIF_4 \u2013 groups are stabilized through intersubunit contacts that are critical for catalysis and the redox centre is repositioned to facilitate electron transfer. Interactions in the nitrogenase complex have broad implications for signal and energy transduction mechanisms in multiprotein complexes.", "date": "1997-05-22", "date_type": "published", "publication": "Nature", "volume": "387", "number": "6631", "publisher": "Nature Publishing Group", "pagerange": "370-376", "id_number": "CaltechAUTHORS:20150617-132613769", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150617-132613769", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)" }, { "agency": "NSF" } ] }, "doi": "10.1038/387370a0", "resource_type": "article", "pub_year": "1997", "author_list": "Schindelin, Hermann; Kisker, Caroline; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/26jzh-cdw60", "eprint_id": 54205, "eprint_status": "archive", "datestamp": "2023-08-19 01:23:15", "lastmod": "2023-10-19 23:45:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Schlessman-J-L", "name": { "family": "Schlessman", "given": "Jamie L." } }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Structure of the ADP\u2022AlF4- stabilized nitrogenase complex and its implications for signal transduction mechanism", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1997 Nature Publishing Group.\n\nReceived 5 December 1996; accepted 26 March 1997.\n\nSupported by the NIH (D.C.R. and J.B.H.), the NSF (J.B.H.) and by Deutsche Forschungsgemeinschaft postdoctoral fellowships (to C.K. and H.S.). X-PLOR calculations were performed on the CRAY C90 at the San Diego Supercomputer Center, supported by the NSF.", "abstract": "The coupling of ATP hydrolysis to electron transfer by the enzyme nitrogenase during biological nitrogen fixation is an important example of a nucleotide-dependent transduction mechanism. The crystal structure has been determined for the complex between the Fe-protein and MoFe-protein components of nitrogenase stabilized by ADP\u00b7AIF4\u2013, previously used as a nucleoside triphosphate analogue in nucleotide-switch proteins. The structure reveals that the dimeric Fe-protein has undergone substantial conformational changes. The \u03b2-phosphate and AIF4\u2013 groups are stabilized through intersubunit contacts that are critical for catalysis and the redox centre is repositioned to facilitate electron transfer. Interactions in the nitrogenase complex have broad implications for signal and energy transduction mechanisms in multiprotein complexes.", "date": "1997-05-22", "date_type": "published", "publication": "Nature", "volume": "387", "publisher": "Nature Publishing Group", "pagerange": "370-376", "id_number": "CaltechAUTHORS:20150128-163948369", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150128-163948369", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)" } ] }, "doi": "10.1038/387370a0", "resource_type": "article", "pub_year": "1997", "author_list": "Schindelin, Hermann; Kisker, Caroline; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f1hck-5tw53", "eprint_id": 52301, "eprint_status": "archive", "datestamp": "2023-08-19 01:21:43", "lastmod": "2023-10-18 19:45:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "M. H. B." } }, { "id": "McPhillips-T-M", "name": { "family": "McPhillips", "given": "T. M." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Soltis-S-M", "name": { "family": "Soltis", "given": "S. M." } }, { "id": "Abresch-E", "name": { "family": "Abresch", "given": "E." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } } ] }, "title": "Light-Induced Structural Changes in Photosynthetic Reaction Center: Implications for Mechanism of Electron-Proton Transfer", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1997 American Association for the Advancement of Science.\n\nReceived 18 September 1996; accepted 10 March 1997.\n\nWe thank M. Y. Okamura, M. L. Paddock, H. L.\nAxelrod, and M. S. Graige for insightful comments\nand discussions. This work was supported by grants\nfrom the National Institutes of Health (NIH GM13191,\nNIH GM45162). The rotation camera facility at SSRL\nis supported by the Department of Energy and by\nNIH. X-PLOR calculations were performed at the\nSan Diego Supercomputer Center supported by\nNSF. The coordinates have been deposited in the\nBrookhaven Protein Data Bank with accession number\n1aig and aij.", "abstract": "High resolution x-ray diffraction data from crystals of theRhodobacter sphaeroides photosynthetic reaction center (RC) have been collected at cryogenic temperature in the dark and under illumination, and the structures were refined at 2.2 and 2.6 angstrom resolution, respectively. In the charge-separated D+Q_AQ_B\u2212 state (where D is the primary electron donor (a bacteriochlorophyll dimer), and Q_A and Q_B are the primary and secondary quinone acceptors, respectively), Q_B\u2212 is located approximately 5 angstroms from the Q_B position in the charge-neutral (DQ_AQ_B) state, and has undergone a 180\u00b0 propeller twist around the isoprene chain. A model based on the difference between the two structures is proposed to explain the observed kinetics of electron transfer from Q_A\u2013Q_B to Q_AQ_B\u2212 and the relative binding affinities of the different ubiquinone species in the Q_B pocket. In addition, several water channels (putative proton pathways) leading from the Q_B pocket to the surface of the RC were delineated, one of which leads directly to the membrane surface.", "date": "1997-05-02", "date_type": "published", "publication": "Science", "volume": "276", "number": "5313", "publisher": "American Association for the Advancement of Science", "pagerange": "812-816", "id_number": "CaltechAUTHORS:20141203-081101674", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141203-081101674", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NSF" } ] }, "doi": "10.1126/science.276.5313.812", "resource_type": "article", "pub_year": "1997", "author_list": "Stowell, M. H. B.; McPhillips, T. M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r9mhb-5rj52", "eprint_id": 54433, "eprint_status": "archive", "datestamp": "2023-08-19 01:11:26", "lastmod": "2023-10-20 16:27:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soltis-S-M", "name": { "family": "Soltis", "given": "S. Michael" } }, { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Wiener-M-C", "name": { "family": "Wiener", "given": "Michael C." } }, { "id": "Phillips-G-N-Jr", "name": { "family": "Phillips", "given": "George N., Jr." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Successful Flash-Cooling of Xenon Derivatized Myoglobin Crystals", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1997 International Union of Crystallography.\n\nReceived 18 July 1996, accepted 16 October 1996.\n\nThis work was supported in part by NIH GM45062 of the NSF to DCR and by the DOE, Office of Basic Energy Sciences and the Office of Health and Environmental Research, and by the NIH, Biomedical Research Technology Program, National\nCenter for Research Resources for support of the rotation camera facilities at SSRL. We thank R. P. Phizackerley and Henry D. Bellamy for helpful discussions.\n\nPublished - 93_soltis_1997.pdf
", "abstract": "This paper demonstrates for the first time a method for preparing cryocooled xenon-derivatized protein crystals. The method is based upon the hypothesis and subsequent observation that the diffusion of a xenon atom from a tight binding site following depressurization occurs on a timescale of minutes. We have observed significant changes in diffraction intensities from myoglobin crystals for up to 5 min following depressurization from 1 MPa of xenon. In accordance with this observation, a xenon-derivatized myoglobin crystal was cryocooled at ~95 K within 20 s of complete depressurization. A crystallographic data set was then collected to 2.0 \u00c5 resolution and isomorphous and anomalous difference Patterson maps revealed the presence of a well ordered xenon site with an occupancy of approximately 0.5. Phasing statistics for this site were of good quality and demonstrate the practicality of this method. The ability to cryocool xenon-derivatized crystals will make this heavy-atom substitution method even more useful for single-isomorphous-replacement and multiple-isomorphous-replacement phasing of macromolecules.", "date": "1997-04", "date_type": "published", "publication": "Journal of Applied Crystallography", "volume": "30", "number": "2", "publisher": "International Union of Crystallography", "pagerange": "190-194", "id_number": "CaltechAUTHORS:20150205-140015180", "issn": "0021-8898", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140015180", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45062" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1107/S0021889896012939", "primary_object": { "basename": "93_soltis_1997.pdf", "url": "https://authors.library.caltech.edu/records/r9mhb-5rj52/files/93_soltis_1997.pdf" }, "resource_type": "article", "pub_year": "1997", "author_list": "Soltis, S. Michael; Stowell, Michael H. B.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yrx4t-24y02", "eprint_id": 47974, "eprint_status": "archive", "datestamp": "2023-08-19 01:03:39", "lastmod": "2023-10-26 21:26:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Peters-J-W", "name": { "family": "Peters", "given": "John W." } }, { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Soltis-S-M", "name": { "family": "Soltis", "given": "S. Michael" } }, { "id": "Finnegan-M-G", "name": { "family": "Finnegan", "given": "Michael G." } }, { "id": "Johnson-M-K", "name": { "family": "Johnson", "given": "Michael K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Redox-Dependent Structural Changes in the Nitrogenase P-Cluster", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1997 American Chemical Society.\n\nReceived October 24, 1996.\n\nDiscussions with J. B. Howard are gratefully acknowledged.\nThis work was supported by NSF DMB 91-18689 (D.C.R.), NIH\nGM51962 (M.K.J.), and an NIH postdoctoral fellowship (GM18142) to J.W.P. The rotation camera facility at the Stanford Synchrotron Radiation Laboratory is supported by the DOE Office of Basic Energy Sciences and the NIH Biomedical Technology Program, Division of\nResearch Resources.", "abstract": "The structure of the nitrogenase MoFe-protein from Azotobacter vinelandii has been refined to 2.0 \u00c5 resolution in two oxidation states. EPR studies on the crystals indicate that the structures correspond to the spectroscopically assigned oxidized (P^(OX)/M^(OX)) and the native or dithionite-reduced (P^(N)/M^(N)) forms of the enzyme. Both MoFe-protein structures are essentially identical, with the exception of the P-cluster. The MoFe-protein P-cluster in each state is found to contain eight Fe and seven S atoms. Interconversion between the two redox states involves movement of two Fe atoms and an exchange of protein coordination for ligands supplied by a central S atom. In the oxidized P^(OX) state, the cluster is coordinated by the protein through six cysteine ligands, Ser-\u03b2188 O\u03b3, and the backbone amide of Cys-\u03b188. In the native P^(N) state, Ser-\u03b2188 O\u03b3 and the amide N of Cys-\u03b188 no longer coordinate the cluster due to movement of their coordinated Fe atoms toward the central sulfur. Consequently, this central sulfur adopts a distorted octahedral environment with six surrounding Fe atoms. A previously described model of the P-cluster containing 8Fe-8S likely reflects the inappropriate modeling of a single structure to a mixture of these two P-cluster redox states. These observed redox-mediated structural changes of the P-cluster suggest a role for this cluster in coupling electron transfer and proton transfer in nitrogenase.", "date": "1997-02-11", "date_type": "published", "publication": "Biochemistry", "volume": "36", "number": "6", "publisher": "American Chemical Society", "pagerange": "1181-1187", "id_number": "CaltechAUTHORS:20140805-113458653", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140805-113458653", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB 91-18689" }, { "agency": "NIH", "grant_number": "GM51962" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "GM18142" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH Biomedical Technology Program" } ] }, "doi": "10.1021/bi9626665", "resource_type": "article", "pub_year": "1997", "author_list": "Peters, John W.; Stowell, Michael H. B.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/w8tw1-ddh23", "eprint_id": 47384, "eprint_status": "archive", "datestamp": "2023-08-19 00:37:06", "lastmod": "2023-10-26 20:32:54", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Peters-J-W", "name": { "family": "Peters", "given": "John W." } }, { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A leucine-rich repeat variant with a novel repetitive protein structural motif", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 Nature Publishing Group.\n\nReceived 20 September; accepted 24 October 1996.\n\nWe thank D. Dean and L. Zheng for the LRV expression plasmid and suggestions on its purification, and the structural biology group at the Stanford Synchrotron Radiation Laboratory (SSRL) for assistance during data collection. This work was supported by a grant from NIH to D. C. R. and an NIH postdoctoral fellowship to J. W. P. The rotation camera facility at SSRL is supported by the DOE Office of Basic Energy Sciences and the NIH Biomedical Research Technology Program, Division of Research Resources.", "abstract": "The structure of the leucine-rich repeat variant protein reveals a novel fold consisting of alternating \u03b1- and 3_(10)-helices arranged in a right-handed superhelix that follows an N-terminal 4Fe:4S cluster-containing domain.", "date": "1996-12", "date_type": "published", "publication": "Nature Structural Biology", "volume": "3", "number": "12", "publisher": "Nature Publishing Group", "pagerange": "991-994", "id_number": "CaltechAUTHORS:20140722-084439321", "issn": "1072-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140722-084439321", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NIH Postdoctoral Fellowship" }, { "agency": "Department of Energy (DOE) Office of Basic Energy Sciences" } ] }, "doi": "10.1038/nsb1296-991", "resource_type": "article", "pub_year": "1996", "author_list": "Peters, John W.; Stowell, Michael H. B.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/041td-dmn24", "eprint_id": 85419, "eprint_status": "archive", "datestamp": "2023-08-19 00:33:32", "lastmod": "2023-10-18 18:12:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Johnson-M-K", "name": { "family": "Johnson", "given": "Michael K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } } ] }, "title": "Tungstoenzymes", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 American Chemical Society. \n\nReceived June 3, 1996 (Revised Manuscript Received August 28, 1996). \n\nResearch carried out in the authors' laboratories was supported by grants from the National Institutes of Health, the National Science Foundation, and the Department of Energy.", "abstract": "Tungsten (W, atomic number 74) and molybdenum\n(Mo, 42) are chemically analogous elements, and both\nare relatively scarce in natural environments. The\nnotion that either of them might have a significant\nbiological role is perhaps surprising when one considers\nthat, with the exception of iodine (53), life forms\non this planet typically thrive by utilizing elements\nwith atomic numbers below 35. Yet, from a biological\nperspective, W and Mo provide a fascinating\nstudy in contrasts. The essential role of Mo in\nvarious fundamental biological conversions carried\nout by both microorganisms and higher (larger) life\nforms has been known for many decades. Molybdoenzymes\nare ubiquitous in nature and play intimate\nroles in the global cycles of nitrogen, carbon,\nand sulfur, with nitrogenase, nitrate reductase, formate\ndehydrogenase, and xanthine oxidase being\nprime and extensively studied examples. On the other hand, W has traditionally been regarded as an\nantagonist of the biological functions of Mo. Because\nof the great similarities in the properties of the two\nelements, it was reasoned that insight into the\ncatalytic role of Mo in various enzymes might be\nprovided by replacing Mo with W. Various\norganisms, including plants and rats, were therefore\ngrown with or exposed to W, but they produced either\ninactive metal-free molybdoenzymes or W-substituted\nenzymes with little or no activity. Clearly,\nthe chemical properties of W and Mo are sufficiently\ndifferent that biology can distinguish between them,\neither at the levels of their uptake and/or incorporation\ninto enzymes or in the properties of the enzymes\nthemselves, which function with Mo but not with W.", "date": "1996-11-07", "date_type": "published", "publication": "Chemical Reviews", "volume": "96", "number": "7", "publisher": "American Chemical Society", "pagerange": "2817-2840", "id_number": "CaltechAUTHORS:20180322-133432851", "issn": "0009-2665", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180322-133432851", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1021/cr950063d", "resource_type": "article", "pub_year": "1996", "author_list": "Johnson, Michael K.; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/8c4cg-em217", "eprint_id": 86255, "eprint_status": "archive", "datestamp": "2023-08-19 00:31:58", "lastmod": "2023-10-18 19:24:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural Basis of Biological Nitrogen Fixation", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 American Chemical Society. \n\nReceived April 26, 1996 (Revised Manuscript Received July 11, 1996) \n\nThe contributions of our group members who made this review possible are greatly appreciated, as are discussions with our nitrogenase colleagues. Research in the authors' laboratory was supported by NSF DMB 91-18689 (D.C.R.), NSF MCB 95-13512 (J.B.H.) and USPHS GM45162 (D.C.R. and J.B.H.).", "abstract": "[no abstract]", "date": "1996-11", "date_type": "published", "publication": "Chemical Reviews", "volume": "96", "number": "7", "publisher": "American Chemical Society", "pagerange": "2965-2982", "id_number": "CaltechAUTHORS:20180507-141345284", "issn": "0009-2665", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180507-141345284", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB 91-18689" }, { "agency": "NSF", "grant_number": "MCB 95-13512" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1021/cr9500545", "resource_type": "article", "pub_year": "1996", "author_list": "Howard, James B. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/38h1s-9cw85", "eprint_id": 48398, "eprint_status": "archive", "datestamp": "2023-08-19 00:22:54", "lastmod": "2023-10-17 18:46:57", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Soltis-S-M", "name": { "family": "Soltis", "given": "S. Michael" } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Peters-J-W", "name": { "family": "Peters", "given": "John W." } }, { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Cascio-D", "name": { "family": "Cascio", "given": "Duilio" } }, { "id": "Beamer-L", "name": { "family": "Beamer", "given": "Lesa" } }, { "id": "Hart-P-J", "name": { "family": "Hart", "given": "P. John" } }, { "id": "Wiener-M-C", "name": { "family": "Wiener", "given": "Michael C." } }, { "id": "Whitby-F-G", "name": { "family": "Whitby", "given": "Frank G." } } ] }, "title": "A simple device for studying macromolecular crystals under moderate gas pressures (0.1-10 MPa)", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1996 International Union of Crystallography. Received 12 December 1995; accepted 9 April 1996. This work was supported in part by NIH GM45062 of the NSF to OCR and by the DOE, Office of Basic Energy Sciences and the Office of Health and Environmental Research, and by the NIH, Biomedical Research Technology Program, National Center for Research Resources for support of the rotation camera facilities at SSRL. JPH is supported by a DOE Alexander Hollaender Distinguished Postdoctoral Fellowship. We wish to thank R. P. Phizackerley for assistance in the design of the gas-delivery system and Hartmut Luecke and Henry D. Bellamy for helpful discussions.\n\nPublished - Stowell_1996p608.pdf
", "abstract": "A simple device for studying crystalline samples under moderate gas pressure (0.1-10 MPa) has been developed. The device employs a modified Cajon ultra-torr fitting to ensure a gas-tight seal around an X-ray capillary. The cell accommodates standard X-ray capillaries that require no modification. The device is straightforward to utilize and samples can be mounted with routine techniques and pressurized in a matter of seconds. In a subsequent development, a complete purging and pressurization system has been designed and constructed for use on beamline 7-1 at the Stanford Synchrotron Radiation Laboratory. This paper describes the construction of both the pressure cell and the delivery system and presents results of the use of this cell for the preparation of xenon derivatives to be used in phase determination by the multiple isomorphous replacement method.", "date": "1996-10", "date_type": "published", "publication": "Journal of Applied Crystallography", "volume": "29", "number": "5", "publisher": "International Union of Crystallography", "pagerange": "608-613", "id_number": "CaltechAUTHORS:20140812-125646031", "issn": "0021-8898", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140812-125646031", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45062" }, { "agency": "NSF" }, { "agency": "NIH" }, { "agency": "Department of Energy (DOE) Alexander Hollaender Distinguished Postdoctoral Fellowship" } ] }, "doi": "10.1107/S0021889896004712", "primary_object": { "basename": "Stowell_1996p608.pdf", "url": "https://authors.library.caltech.edu/records/38h1s-9cw85/files/Stowell_1996p608.pdf" }, "resource_type": "article", "pub_year": "1996", "author_list": "Stowell, Michael H. B.; Soltis, S. Michael; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/03xa9-75g74", "eprint_id": 53637, "eprint_status": "archive", "datestamp": "2023-08-19 00:00:57", "lastmod": "2023-10-19 21:57:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Hilton-J", "name": { "family": "Hilton", "given": "James" } }, { "id": "Rajagopalan-K-V", "name": { "family": "Rajagopalan", "given": "K. V." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal Structure of DMSO Reductase: Redox-Linked Changes in Molybdopterin Coordination", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 American Association for the Advancement of Science.\n\n15 January 1996: Accepted 23 April 1996.\n\nWe thank J. Enemark for insightful discussions and\nsuggestions on the manuscript. Supported by Deutsche\nForschungsgemeinschaft postdoctoral fellowships\n(to C.K. and H.S.), by USPHS grant GM50775\n(D.C.R.), and by USPHS grant GM00091 (K.V.R.).\nThe rotation camera facility at SSRL is supported by\nthe Department of Energy and NIH. The X-PLOR\ncalculations were performed on the CRAY C90 at the\nSan Diego Supercomputer Center, supported by the\nNSF. Coordinates have been deposited in the\nBrookhaven Protein Data Bank and can be supplied\nby e-mail to hermann@citray.caltech.edu.", "abstract": "The molybdoenzyme dimethylsulfoxide (DMSO) reductase contributes to the release of dimethylsulfide, a compound that has been implicated in cloud nucleation and global climate regulation. The crystal structure of DMSO reductase from Rhodobacter sphaeroides reveals a monooxo molybdenum cofactor containing two molybdopterin guanine dinucleotides that asymmetrically coordinate the molybdenum through their dithiolene groups. One of the pterins exhibits different coordination modes to the molybdenum between the oxidized and reduced states, whereas the side chain oxygen of Ser^(147) coordinates the metal in both states. The change in pterin coordination between the Mo(VI) and Mo(IV) forms suggests a mechanism for substrate binding and reduction by this enzyme. Sequence comparisons of DMSO reductase with a family of bacterial oxotransferases containing molybdopterin guanine dinucleotide indicate a similar polypeptide fold and active site with two molybdopterins within this family.", "date": "1996-06-14", "date_type": "published", "publication": "Science", "volume": "272", "number": "5268", "publisher": "American Association for the Advancement of Science", "pagerange": "1615-1621", "id_number": "CaltechAUTHORS:20150113-144809357", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150113-144809357", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Deutsche Forschungsgemeinschaft (DFG)" }, { "agency": "USPHS", "grant_number": "GM50775" }, { "agency": "USPHS", "grant_number": "GM00091" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NIH" }, { "agency": "NSF" } ] }, "collection": "CaltechAUTHORS", "doi": "10.1126/science.272.5268.1615", "resource_type": "article", "pub_year": "1996", "author_list": "Schindelin, Hermann; Kisker, Caroline; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gpe88-gaa88", "eprint_id": 54436, "eprint_status": "archive", "datestamp": "2023-08-22 11:03:03", "lastmod": "2023-10-20 16:27:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kisker-C", "name": { "family": "Kisker", "given": "Caroline" } }, { "id": "Schindelin-H", "name": { "family": "Schindelin", "given": "Hermann" } }, { "id": "Alber-B-E", "name": { "family": "Alber", "given": "Birgit E." } }, { "id": "Ferry-J-G", "name": { "family": "Ferry", "given": "James G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A Left-handed \u03b2 Helix Revealed by the Crystal Structure of a Carbonic Anhydrase from the Archaeon Methanosarcina thermophila", "ispublished": "pub", "full_text_status": "public", "keywords": "archaea; carbonic anhydrase; convergent evolution; left-handed \u03b2-helix", "note": "\u00a9 1996 Oxford University Press.\n\nReceived on November 17, 1995; revised on January 9, 1996.\n\nThe authors would like to thank Dr Joachim Behlke for carrying out the\nanalytical ultracentrifugation experiments. This work was supported by\nDeutsche Forschungsgemeinschaft postdoctoral fellowships (to C.K. and\nH.S.), by USPHS and NSF grants (to D.C.R.) and by an NIH grant (to\nJ.G.F.). The rotation camera facility at SSRL is supported by DOE and NIH. Coordinates have been deposited in the Protein Data Bank PDBID\ncode ITHJ, they can also be requested by E-mail to kisker@citray.caltech.edu.\n\nPublished - 84_kisker_1996.pdf
", "abstract": "A carbonic anhydrase from the thermophilic archaeon Methanosarcina thermophila that exhibits no significant sequence similarity to known carbonic anhydrases has recently been characterized. Here we present the structure of this enzyme, which adopts a left-handed parallel \u03b2-helix fold. This fold is of particular interest since it contains only left-handed crossover connections between the parallel \u03b2-strands, which so far have been observed very infrequently. The active form of the enzyme is a trimer with three zinc-containing active sites, each located at the interface between two monomers. While the arrangement of active site groups differs between this enzyme and the carbonic anhydrases from higher vertebrates, there are structural similarities in the zinc coordination environment, suggestive of convergent evolution dictated by the chemical requirements for catalysis of the same reaction. Based on sequence similarities, the structure of this enzyme is the prototype of a new class of carbonic anhydrases with representatives in all three phylogenetic domains of life.", "date": "1996-05-15", "date_type": "published", "publication": "EMBO Journal", "volume": "15", "number": "10", "publisher": "European Molecular Biology Organization", "pagerange": "2323-2330", "id_number": "CaltechAUTHORS:20150205-140358415", "issn": "0261-4189", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140358415", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Deutsche Forschungsgemeinschaft (DFG)" }, { "agency": "U.S. Public Health Service (USPHS)" }, { "agency": "NSF" }, { "agency": "NIH" }, { "agency": "Department of Energy (DOE)" } ] }, "pmcid": "PMC450161", "primary_object": { "basename": "84_kisker_1996.pdf", "url": "https://authors.library.caltech.edu/records/gpe88-gaa88/files/84_kisker_1996.pdf" }, "resource_type": "article", "pub_year": "1996", "author_list": "Kisker, Caroline; Schindelin, Hermann; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n2hfd-1b394", "eprint_id": 54435, "eprint_status": "archive", "datestamp": "2023-08-20 07:28:17", "lastmod": "2023-10-20 16:27:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "McPhillips-T-M", "name": { "family": "McPhillips", "given": "Timothy M." } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "Barbara T." } }, { "id": "Sherman-M-A", "name": { "family": "Sherman", "given": "Mark A." } }, { "id": "Mas-M-T", "name": { "family": "Mas", "given": "Maria T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of the R65Q Mutant of Yeast 3-Phosphoglycerate Kinase Complexed with Mg-AMP-PNP and 3-Phospho-d-glycerate", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 American Chemical Society.\n\nReceived October 19, 1995; Revised Manuscript Received January 26, 1996.\n\nSupported in part by NIH Grants GM45162 (D.C.R.) and GM37715 (M.T.M.). T.M.M. was supported in part by NIH Predoctoral Training Grant GM07616.\n\nThe authors thank Dr. Colin F. Blake (Oxford) for providing the unpublished atomic coordinates (porcine PGK, 2.0 \u00c5 resolution; equine PGK, 2.5 \u00c5 resolution) used in the comparative studies. M.T.M. thanks Dr. J. Kraut (UCSD)\nand members of his laboratory for hospitality and training in protein crystallization. T.M.M. thanks Ruth Ann Bertsch for invaluable discussions and editing of the manuscript.", "abstract": "The structure of a ternary complex of the R65Q mutant of yeast 3-phosphoglycerate kinase (PGK) with magnesium 5'-adenylylimidodiphosphate (Mg-AMP-PNP) and 3-phospho-d-glycerate (3-PG) has been determined by X-ray crystallography to 2.4 \u00c5 resolution. The structure was solved by single isomorphous replacement, anomalous scattering, and solvent flattening and has been refined to an R-factor of 0.185, with rms deviations from ideal bond distance and angles of 0.009 \u00c5 and 1.78\u00b0, respectively. PGK consists of two domains, with the 3-PG bound to a \"basic patch\" of residues from the N-terminal domain and the Mg-AMP-PNP interacting with residues from the C-terminal domain. The two ligands are separated by \u223c11 \u00c5 across the interdomain cleft. The model of the R65Q mutant of yeast PGK is very similar to the structures of PGK isolated from horse, pig, and Bacillus stearothermophilus (rms deviations between equivalent \u03b1-carbons in the individual domains < 1.0 \u00c5) but exhibits substantial variations with a previously reported yeast structure (rms deviations between equivalent \u03b1-carbons in the individual domains of 2.9\u22123.2 \u00c5). The most significant tertiary structural differences among the yeast R65Q, equine, porcine, and B. stearothermophilus PGK structures occur in the relative orientations of the two domains. However, the relationships between the observed conformations of PGK are inconsistent with a \"hinge-bending\" behavior that would close the interdomain cleft. It is proposed that the available structural and biochemical data on PGK may indicate that the basic patch primarily represents the site of anion activation and not the catalytically active binding site for 3-PG.", "date": "1996-04-02", "date_type": "published", "publication": "Biochemistry", "volume": "35", "number": "13", "publisher": "American Chemical Society", "pagerange": "4118-4127", "id_number": "CaltechAUTHORS:20150205-140310848", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140310848", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "GM37715" }, { "agency": "NIH", "grant_number": "GM07616" } ] }, "doi": "10.1021/bi952500o", "resource_type": "article", "pub_year": "1996", "author_list": "McPhillips, Timothy M.; Hsu, Barbara T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/8fzk8-4qr08", "eprint_id": 53136, "eprint_status": "archive", "datestamp": "2023-08-20 07:17:48", "lastmod": "2023-10-19 14:35:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Faham-S", "name": { "family": "Faham", "given": "S." } }, { "id": "Hileman-R-E", "name": { "family": "Hileman", "given": "R. E." } }, { "id": "Fromm-J-R", "name": { "family": "Fromm", "given": "J. R." } }, { "id": "Linhard-R-J", "name": { "family": "Linhard", "given": "R. J." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Heparin Structure and Interactions with Basic Fibroblast Growth Factor", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 American Association for the Advancement of Science.\n\n19 September 1995; Accepted 12 December 1995.\n\nWe thank T. Arakawa and G. M. Fox of Amgen for discussions and a generous supply of bFGF and D. Bar-Shalom for stimulating conversations. This work was funded in part by a gift from Amgen and U.S. Public Health Service (USPHS) grant GM38060(R.J.L.), with partial support of the x-ray facility provided by the Beckman Institute at California Institute of Technology and USPHS grant GM45162 (D.C.R.).\nS.F. was supported by USPHS Biotechnology Training grant T32 GM08346.", "abstract": "Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174\u00b0 and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135; the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.", "date": "1996-02-23", "date_type": "published", "publication": "Science", "volume": "271", "number": "5252", "publisher": "American Association for the Advancement of Science", "pagerange": "1116-1120", "id_number": "CaltechAUTHORS:20141223-090448077", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141223-090448077", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Amgen" }, { "agency": "U.S. Public Health Service (USPHS)", "grant_number": "GM38060" }, { "agency": "Caltech Beckman Institute" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "T32 GM08346" } ] }, "doi": "10.1126/science.271.5252.1116", "resource_type": "article", "pub_year": "1996", "author_list": "Faham, S.; Hileman, R. E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7x8qm-cx234", "eprint_id": 54437, "eprint_status": "archive", "datestamp": "2023-08-20 07:10:19", "lastmod": "2023-10-20 16:27:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Rock-R-S", "name": { "family": "Rock", "given": "Ronald S." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Chan-S-I", "name": { "family": "Chan", "given": "Sunney I." }, "orcid": "0000-0002-5348-2723" } ] }, "title": "Efficient Synthesis of Photolabile Alkoxy Benzoin Protecting Groups", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1996 Elsevier Science Ltd.\n\nReceived in USA 7 September 1995; revised 7 November 1995; accepted 10 November 1995.\n\nWe thank Prof. E. M. Carreira for helpful discussions and critical reading of this\nmanuscript. This work was supported by NIH grant GM 22432 from the National Institute of General Medical Sciences, U.S. Public Health Service. Contribution number 9139.", "abstract": "An effective implementation of the Corey-Seebach dithiane addition for the synthesis of photolabile alkoxy benzoin adducts is reported. The method allows for the facile synthesis of photolabile 3\u2032,5\u2032-dimethoxybenzoin protected compounds in near quantitative yield and is general in that it can be used for the synthesis of both symmetrical and unsymmetrical benzoins. Importantly, the dithiane intermediate reported is a versatile starting material for the synthesis of many photolabile compounds and should serve as a useful protecting group in complex synthetic schemes requiring multiple orthogonal protecting groups.", "date": "1996-01-15", "date_type": "published", "publication": "Tetrahedron Letters", "volume": "37", "number": "3", "publisher": "Elsevier", "pagerange": "307-310", "id_number": "CaltechAUTHORS:20150205-140522838", "issn": "0040-4039", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140522838", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 22432" }, { "agency": "National Institute of General Medical Sciences" } ] }, "other_numbering_system": { "items": [ { "id": "9139", "name": "Caltech Arthur Amos Noyes Laboratory" } ] }, "doi": "10.1016/0040-4039(95)02159-0", "resource_type": "article", "pub_year": "1996", "author_list": "Stowell, Michael H. B.; Rock, Ronald S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2h1ch-9qg34", "eprint_id": 52455, "eprint_status": "archive", "datestamp": "2023-08-20 06:13:16", "lastmod": "2023-10-18 19:53:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Joshua-Tor-L", "name": { "family": "Joshua-Tor", "given": "Leemor" } }, { "id": "Xu-H-E", "name": { "family": "Xu", "given": "H. Eric" } }, { "id": "Johnston-S-A", "name": { "family": "Johnston", "given": "Stephen Albert" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1995 American Association for the Advancement of Science.\n\nReceived 3 March 1995; accepted 7 July 1995.\n\nWe thank M. Stowell for help in synchrotron data\ncollection; W. Zheng for discussions and unpublished\nresults; members of the Stanford Synchrotron\nRadiation Laboratory (SSRL) and the Cornell High\nEnergy Synchrotron Source (CHESS) for assistance\nduring data collection; A. Wu for the sedimentation\nexperiments and mass spectometry; K. Swiderek for\nsequencing; R. Huber for coordinates of human cathepsin\nB, and W. Saenger and R. Hilgenfeld for\ncoordinates of calotropin. Supported in part by the\nCaltech Consortium in Chemistry and Chemical Engineering\n(L.J. and D.C.R.), grants from NIH\n(GM40700) and Human Frontier Science Program\n(S.A.J.), and by a postdoctoral fellowship from the\nJane Coffin Childs Memorial Fund for Medical Research\n(L.J.). The diffraction facility was supported in\npart by USPHS grant GM45162 and the Beckman\nInstitute (D.C.R.), and the Howard Hughes Medical\nInstitute (to P. J. Bjorkman). The rotation camera\nfacility at the Stanford Synchrotron Radiation Laboratory\nis supported by the Department of Energy,\nOffice of Basic Energy Sciences and the National\nInstitutes of Health Biomedical Research Technology\nProgram, Division of Research Resources.\nX-PLOR calculations were done on the CRAY C90 at\nthe San Diego Supercomputer Center, supported by\nthe NSF. Coordinates have been deposited in the\nBrookhaven Data Bank (IGCB) and are available by\ne-mail (leemor@citray.caltech.edu).", "abstract": "Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug bleomycin. The homolog in yeast, Gal6, has recently been identified and found to bind DNA and to act as a repressor in the Gal4 regulatory system. The crystal structure of Gal6 at 2.2 \u00c5 resolution reveals a hexameric structure with a prominent central channel. The papain-like active sites are situated within the central channel, in a manner resembling the organization of active sites in the proteasome. The Gal6 channel is lined with 60 lysine residues from the six subunits, suggesting a role in DNA binding. The carboxyl-terminal arm of Gal6 extends into the active site cleft and may serve a regulatory function. Rather than each residing in distinct, separable domains, the protease and DNA-binding activities appear structurally intertwined in the hexamer, implying a coupling of these two activities.", "date": "1995-08-18", "date_type": "published", "publication": "Science", "volume": "269", "number": "5226", "publisher": "American Association for the Advancement of Science", "pagerange": "945-950", "id_number": "CaltechAUTHORS:20141208-090927193", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141208-090927193", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Consortium in Chemistry and Chemical Engineering" }, { "agency": "NIH", "grant_number": "GM40700" }, { "agency": "Human Frontier Science Program" }, { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" }, { "agency": "USPHS", "grant_number": "GM45162" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Department of Energy (DOE)" }, { "agency": "NSF" } ] }, "doi": "10.1126/science.7638617", "resource_type": "article", "pub_year": "1995", "author_list": "Joshua-Tor, Leemor; Xu, H. Eric; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ed0dq-07g46", "eprint_id": 54440, "eprint_status": "archive", "datestamp": "2023-08-20 06:09:12", "lastmod": "2023-10-20 16:27:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kletzin-A", "name": { "family": "Kletzin", "given": "Arnulf" } }, { "id": "Mukund-S", "name": { "family": "Mukund", "given": "Swarnalatha" } }, { "id": "Kelley-Crouse-T-L", "name": { "family": "Kelley-Crouse", "given": "Terry L." } }, { "id": "Chan-M-K", "name": { "family": "Chan", "given": "Michael K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } } ] }, "title": "Molecular characterization of the genes encoding the tungsten-containing aldehyde ferredoxin oxidoreductase from Pyrococcus furiosus and formaldehyde ferredoxin oxidoreductase from Thermococcus litoralis", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1995 American Society for Microbiology. \n\nReceived 21 February 1995; Accepted 8 June 1995. \n\nThis research was supported by grants (to M.W.W.A.) from the Office of Naval Research (N00014-90-J-1894), the Department of Energy (FG09-88ER13901), and the National Science Foundation (BCS-9320069) and by a grant (to D.C.R.) from the National Institutes of Health (GM 50775).\n\nPublished - 80_kletzin_1995.pdf
", "abstract": "The hyperthermophilic archaea Pyrococcus furiosus and Thermococcus litoralis contain the tungstoenzymes aldehyde ferredoxin oxidoreductase, a homodimer, and formaldehyde ferredoxin oxidoreductase, a homotetramer. herein we report the cloning and sequencing of the P. furiosus gene aor (605 residues; M_r, 66,630) and the T. litoralis gene for (621 residues; M_r, 68,941).", "date": "1995-08", "date_type": "published", "publication": "Journal of Bacteriology", "volume": "177", "number": "16", "publisher": "American Society for Microbiology", "pagerange": "4817-4819", "id_number": "CaltechAUTHORS:20150205-140806380", "issn": "0021-9193", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140806380", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-90-J-1894" }, { "agency": "Department of Energy (DOE)", "grant_number": "FG09-88ER13901" }, { "agency": "NSF", "grant_number": "BCS-9320069" }, { "agency": "NIH", "grant_number": "GM 50775" } ] }, "pmcid": "PMC177251", "primary_object": { "basename": "80_kletzin_1995.pdf", "url": "https://authors.library.caltech.edu/records/ed0dq-07g46/files/80_kletzin_1995.pdf" }, "resource_type": "article", "pub_year": "1995", "author_list": "Kletzin, Arnulf; Mukund, Swarnalatha; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wyx66-mtg30", "eprint_id": 54438, "eprint_status": "archive", "datestamp": "2023-08-22 10:30:25", "lastmod": "2023-10-20 16:27:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Arakawa-Tsutomu", "name": { "family": "Arakawa", "given": "Tsutomu" } }, { "id": "Holst-P", "name": { "family": "Holst", "given": "Paige" } }, { "id": "Narhi-L-O", "name": { "family": "Narhi", "given": "Linda O." } }, { "id": "Philo-J-S", "name": { "family": "Philo", "given": "John S." } }, { "id": "Wen-Jie", "name": { "family": "Wen", "given": "Jie" } }, { "id": "Prestrelski-S-J", "name": { "family": "Prestrelski", "given": "Steven J." } }, { "id": "Zhu-Xiaotian", "name": { "family": "Zhu", "given": "Xiaotian" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Fox-G-M", "name": { "family": "Fox", "given": "Gary M." } } ] }, "title": "The importance of Arg40 and 45 in the mitogenic activity and structural stability of basic fibroblast growth factor: Effects of acidic amino acid substitutions", "ispublished": "pub", "full_text_status": "restricted", "keywords": "bFGF; heparin; sucrose octasulfate", "note": "\u00a9 1995 Plenum Publishing Corporation.\n\nReceived January 4, 1995.", "abstract": "High-affinity binding of basic fibroblast growth factor (bFGF) to the tyrosine kinase receptor requires cell-surface heparan sulfate proteoglycan or exogenous addition of heparin. The crystal structure of bFGF shows Arg40 and 45 on the surface opposite to the heparin-binding region, suggesting that these charged residues may be involved in the receptor binding. Therefore, these amino acids were mutated to aspartic acid separately or simultaneously, and also a simultaneous mutation to glutamic acid was introduced. These mutants displayed a mitogenic activity decreased greater than tenfold compared to the wild-type protein. Addition of heparin had no effect on the activity, while these mutants showed heparin-binding characteristics resembling those of the native sequence protein. The mutants exhibited decreased stability compared to the native sequence protein. Gradual changes in conformation were observed by circular dichroic and infrared spectroscopy. Heparin chromatography also showed the presence of denatured form for these mutants. However, in the presence of multivalent anions such as citrate, sucrose octasulfate, and heparin, the conformation of the mutants resembled that of the wild-type protein, as revealed by X-ray crystallography and circular dichroism spectra of the mutant with a Arg40 \u2192 Asp substitution.", "date": "1995-07", "date_type": "published", "publication": "Journal of Protein Chemistry", "volume": "14", "number": "5", "publisher": "Springer", "pagerange": "263-274", "id_number": "CaltechAUTHORS:20150205-140649548", "issn": "0277-8033", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140649548", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1007/BF01886783", "resource_type": "article", "pub_year": "1995", "author_list": "Arakawa, Tsutomu; Holst, Paige; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/trc5j-2k587", "eprint_id": 54443, "eprint_status": "archive", "datestamp": "2023-08-20 05:37:30", "lastmod": "2023-10-20 16:28:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } } ] }, "title": "Hyperthermophiles: Taking the Heat and Loving It", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1995 Current Biology Ltd.\n\nSupport for experimental work was provided by NSF (DMB 91-18689) and USPHS (GM50775) for DCR's work and by ONR (N00014-90-J-1894), DOE (FG09-88ER13901) and NSF (BCS-9320069) for MWWA's work.", "abstract": "Hyperthermophiles, a recently discovered group of microorganisms, are operationally defined as having an optimum growth temperature of at least 80\u00b0C and a maximum growth temperature of over 90\u00b0C. Most of the enzymes isolated so far from such organisms exhibit correspondingly enhanced thermostability. This property has been used both for investigation of fundamental biological questions of protein structure and stability, and for the development of technological applications that require protein stability at high temperatures. Examples of such applications of thermostable proteins include their use in biocatalysts, in various materials and in crystallization methods. The use of DNA polymerases from hyperthermophilic microorganisms in the polymerase chain reaction (PCR) is another of the more practical examples of the recent impact on biochemistry and molecular biology of enzymes isolated from hyperthermophilic organisms.\n\nTo date, the maximum growth temperatures observed for a hyperthermophilic organism is about 110\u00b0C. Whether this is the upper limit for life is unknown; some workers estimate that the maximum growth temperature for, as yet, uncultured organisms may approach, or even exceed 150\u00b0C [1]. In any event, it is clear that the surface has barely been scratched in the study of extremely thermostable proteins from known hyperthermophiles. Two basic questions often come to mind when considering these enzymes: the practically motivated, how can I get some of these enzymes and the more fundamental question, how do these enzymes achieve extreme thermostability? Aspects of both of these issues are briefly discussed below. More detailed discussions of hyperthermophiles and their proteins may be found in review articles [2], [3], [4] and [5].", "date": "1995-03-15", "date_type": "published", "publication": "Structure", "volume": "3", "number": "3", "publisher": "Cell Press", "pagerange": "251-254", "id_number": "CaltechAUTHORS:20150205-140919633", "issn": "0969-2126", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-140919633", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB 91-18689" }, { "agency": "U.S. Public Health Serivce", "grant_number": "GM50775" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-90-J-1894" }, { "agency": "Department of Energy (DOE)", "grant_number": "FG09-88ER13901" }, { "agency": "NSF", "grant_number": "BCS-9320069" } ] }, "doi": "10.1016/S0969-2126(01)00155-1", "resource_type": "article", "pub_year": "1995", "author_list": "Rees, Douglas C. and Adams, Michael W. W." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wsen4-dke26", "eprint_id": 53944, "eprint_status": "archive", "datestamp": "2023-08-20 05:36:40", "lastmod": "2023-10-19 22:25:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chan-M-K", "name": { "family": "Chan", "given": "Michael K." } }, { "id": "Mukund-S", "name": { "family": "Mukund", "given": "Swarnalatha" } }, { "id": "Kletzin-A", "name": { "family": "Kletzin", "given": "Arnulf" } }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1995 American Association for the Advancement of Science.\n\n30 September 1994; Accepted 20 January 1995.\n\nWe thank B. T. Hsu, J. Schlessman, J. Kim, S. Faham, M. Stowell, and T. McPhillips for advice and assistance, and A. G. Myers, M. K. Johnson, P. J. Bjorkman, and J. E. Bercaw for discussions. Supported by USPHS grant GM50775 (D.C.R.); ONR grant N00014-90-J-1894 (M.W.W.A.), DOE grant\nFG09-88ER1 3901 (M.W.W.A.) and NSF grant BCS-9320069 (M.W.W.A.); the Beckman Institute, the Joseph Irvine Equipment Fund, and the Howard Hughes Medical Institute (to P. J. Bjorkman) for part of the diffraction instrumentation; NIH fellowship 1F32 GM1 5006 (M.K.C.); and by the rotation camera facility at the Stanford Synchrotron Radiation Laboratory, which in tum is supported by the Department of Energy, Office of Basic Energy Sciences,\nand the National Institutes of Health Biomedical Resource\nTechnology Program, Division of Research Resources. Coordinates have been deposited in the Brookhaven Protein Data base, not yet available.", "abstract": "The crystal structure of the tungsten-containing aldehyde ferredoxin oxidoreductase (AOR) from Pyrococcus furiosus, a hyperthermophilic archaeon (formerly archaebacterium) that grows optimally at 100 degrees C, has been determined at 2.3 angstrom resolution by means of multiple isomorphous replacement and multiple crystal form averaging. AOR consists of two identical subunits, each containing an Fe4S4 cluster and a molybdopterin-based tungsten cofactor that is analogous to the molybdenum cofactor found in a large class of oxotransferases. Whereas the general features of the tungsten coordination in this cofactor were consistent with a previously proposed structure, each AOR subunit unexpectedly contained two molybdopterin molecules that coordinate a tungsten by a total of four sulfur ligands, and the pterin system was modified by an intramolecular cyclization that generated a three-ringed structure. In comparison to other proteins, the hyperthermophilic enzyme AOR has a relatively small solvent-exposed surface area, and a relatively large number of both ion pairs and buried atoms. These properties may contribute to the extreme thermostability of this enzyme.", "date": "1995-03-10", "date_type": "published", "publication": "Science", "volume": "267", "number": "5203", "publisher": "American Association for the Advancement of Science", "pagerange": "1463-1469", "id_number": "CaltechAUTHORS:20150121-112458293", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150121-112458293", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "United States Public Health Service (USPHS)", "grant_number": "GM50775" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-90-J-1894" }, { "agency": "Department of Energy (DOE)", "grant_number": "FG09-88ER13901" }, { "agency": "NSF", "grant_number": "BCS-9320069" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Joseph Irvine Equipment Fund" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "1F32 GM15006" } ] }, "doi": "10.1126/science.7878465", "resource_type": "article", "pub_year": "1995", "author_list": "Chan, Michael K.; Mukund, Swarnalatha; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fec72-6mt74", "eprint_id": 54445, "eprint_status": "archive", "datestamp": "2023-08-20 05:07:15", "lastmod": "2023-10-20 16:28:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure and Stability of Membrane Proteins", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1995 Academic Press.\n\nAvailable online 14 April 2008.\n\nWe thank our colleagues/collaborators SJ. Chan, D.S. Eisenberg, and G. Feher for\nsharing their insights into membrane proteins; W. K\u00fchlbrapdt for providing LHCII coordinates; and NIH GM45162 for support.", "abstract": "This chapter addresses question such as \"If the hydrophobic theory of protein stability is correct, how is it possible for stable proteins to exist in nonaqueous environments where hydrophobic effects should be quantitatively less significant?\" in light of the available structural and stability data on integral membrane proteins, emphasizing a comparison of these properties to those of better characterized water-soluble proteins. An important lesson from the study of membrane proteins is that water is not absolutely indispensable for the ability of proteins to adopt stable three-dimensional structures; proteins can also stably exist in nonaqueous solvents, whether in the membrane bilayer or in nonbiological systems. By definition, hydrophobic interactions are not indispensable for protein stability, because proteins with stable tertiary structures occur in nonaqueous solvents. The role of hydrophobic interactions in protein stability may be analogous to the role of disulfide bridges; whereas some proteins cannot exist without disulfide bridges, they are certainly not required by every protein. The continued study of proteins in membranes and other nonaqueous environments is fundamental to defining the contributions of all solvents to the origins of protein structure and stability.", "date": "1995", "date_type": "published", "publication": "Advances in Protein Chemistry", "volume": "46", "publisher": "Elsevier", "pagerange": "279-311", "id_number": "CaltechAUTHORS:20150205-141101496", "issn": "0065-3233", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141101496", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1016/S0065-3233(08)60338-1", "resource_type": "article", "pub_year": "1995", "author_list": "Stowell, Michael H. B. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0ry1z-t2g53", "eprint_id": 1624, "eprint_status": "archive", "datestamp": "2023-08-22 09:58:17", "lastmod": "2023-10-13 22:54:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase: A nucleotide-dependent molecular switch", "ispublished": "pub", "full_text_status": "public", "keywords": "NITROGEN FIXATION; NUCLEOTIDE-BINDING PROTEINS; ADP/ATP; ENZYME MECHANISM; METAL CLUSTERS; IRON-MOLYBDENUM COFACTOR; AZOTOBACTER-VINELANDII NITROGENASE; MAGNESIUM ADENOSINE 5'-TRIPHOSPHATE; ELECTRON-PARAMAGNETIC RESONANCE; SUBSTRATE REDUCTION PROPERTIES; KLEBSIELLA-PNEUMONIAE; FE-PROTEIN; CLOSTRIDIUM-PASTEURIANUM; HYDROGEN EVOLUTION; MOFE-PROTEIN", "note": "\"Reprinted, with permission, from the Annual Review of Biochemistry, Volume 63 copyright 1994 by Annual Reviews, www.annualreviews.org\" \n\nThe efforts and contributions of J. Kim, M. Georgiadis, D. Woo, M. K. Chart, M. W. Day, J. Schlessman, H. Komiya, L. Joshua-Tot, M. H. B. Stowell, B. T. Hsu and A. J. Chirino are deeply appreciated, as are discussions, sharing of preprints, etc with our nitrogenase colleagues. Research in the authors' laboratories was supported by grants from NIH and NSF.", "abstract": "In the simplest terms, the biological nitrogen cycle is the reduction of atmospheric dinitrogen (N2) to ammonia with the subsequent reoxidation ammonia to dinitrogen (1). At the reduction level of ammonia, nitrogen incorporated into precursors for biological macromolecules such as proteins and nucleic acids. Reoxidation of ammonia to dinitrogen (\"denitrification\") by a variety of microbes (by way of nitrite and other oxidation levels of nitrogen) leads to the depletion of the \"fixed,\" biologically usable, nitrogen pool. Besides the relatively small contribution from commercial ammonical fertilizer production, replenishing of the nitrogen pool falls mainly to a limited number of physiologically diverse microbes (e.g. eubacteria and archaebacteria; free-living and symbiotic; aerobic and anaerobic) that contain the nitrogenase enzyme system.", "date": "1994-07-01", "date_type": "published", "publication": "Annual Review of Biochemistry", "volume": "63", "publisher": "Annual Review of Biochemistry", "pagerange": "235-264", "id_number": "CaltechAUTHORS:HOWarb94", "issn": "0066-4154", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:HOWarb94", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1146/annurev.bi.63.070194.001315", "primary_object": { "basename": "HOWarb94.pdf", "url": "https://authors.library.caltech.edu/records/0ry1z-t2g53/files/HOWarb94.pdf" }, "resource_type": "article", "pub_year": "1994", "author_list": "Howard, James B. and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/j6etr-yv736", "eprint_id": 54446, "eprint_status": "archive", "datestamp": "2023-08-20 04:25:07", "lastmod": "2023-10-20 16:28:29", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Axelrod-H-L", "name": { "family": "Axelrod", "given": "Herbert L." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "George" } }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "James P." } }, { "id": "Chirino-A-J", "name": { "family": "Chirino", "given": "Arthur J." } }, { "id": "Day-M-W", "name": { "family": "Day", "given": "Michael W." } }, { "id": "Hsu-Barbara-T", "name": { "family": "Hsu", "given": "Barbara T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystallization and X-ray Structure Determination of Cytochrome c_2 from Rhodobacter sphaeroides in Three Crystal Forms", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1994 International Union of Crystallography.\n\nReceived 15 November 1993; accepted 31 January 1994.\n\nPublished - 75_axelrod_1994.pdf
", "abstract": "Cytochrome c_2 serves as the secondary electron donor that reduces the photo-oxidized bacteriochlorophyll dimer in photosynthetic bacteria. Cytochrome c_2 from Rhodobacter sphaeroides has been crystallized in three different forms. At high ionic strength, crystals of a hexagonal space group (P6_122) were obtained, while at low ionic strength, triclinic (P1) and tetragonal (P4_12_12) crystals were formed. The three-dimensional structures of the cytochrome in all three crystal forms have been determined by X-ray diffraction at resolutions of 2.20 \u00c5 (hexagonal), 1.95 \u00c5, (triclinic) and 1.53 \u00c5 (tetragonal). The most significant difference observed was the binding of an imidazole molecule to the iron atom of the heme group in the hexagonal structure. This binding displaces the sulfur atom of Met 100, which forms the axial ligand in the triclinic and tetragonal structures.", "date": "1994-07", "date_type": "published", "publication": "Acta Crystallographica Section D: Biological Crystallography", "volume": "50", "number": "4", "publisher": "International Union of Crystallography", "pagerange": "596-602", "id_number": "CaltechAUTHORS:20150205-141153331", "issn": "0907-4449", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141153331", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1107/S0907444994001319", "primary_object": { "basename": "75_axelrod_1994.pdf", "url": "https://authors.library.caltech.edu/records/j6etr-yv736/files/75_axelrod_1994.pdf" }, "resource_type": "article", "pub_year": "1994", "author_list": "Axelrod, Herbert L.; Feher, George; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rsvk4-qqc47", "eprint_id": 54447, "eprint_status": "archive", "datestamp": "2023-08-20 04:10:43", "lastmod": "2023-10-20 16:28:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chirino-A-J", "name": { "family": "Chirino", "given": "Arthur J." } }, { "id": "Lous-E-J", "name": { "family": "Lous", "given": "Erik J." } }, { "id": "Huber-M", "name": { "family": "Huber", "given": "Martina" } }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "James P." } }, { "id": "Schenck-C-C", "name": { "family": "Schenck", "given": "Craig C." } }, { "id": "Paddock-M-L", "name": { "family": "Paddock", "given": "Mark L." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "George" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystallographic Analyses of Site-Directed Mutants of the Photosynthetic Reaction Center from Rhodobacter sphaeroides", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1994 American Chemical Society.\n\nReceived September 21, 1993; Revised Manuscript Received February 7, 1994.\n\nThis work was supported by the National Institutes of Health (GM45162 to D.C.R., GM41300 to J.P.A., GM13191 to G.F., GM41637 to M.L.P., and R.C.D.A. GM00536 and GM38214/48254 to C.C.S.). E.J.L. was supported by the European Molecular Biology Organisation and M.H. by a Forschungsstipendium of the Deutsche Forschungsgemeinschaft.\n\nUse of the X-ray data collection facilities at UCLA and the Cray YMP at the National Science Foundation-supported San Diego Supercomputer Center is gratefully acknowledged.", "abstract": "Seven site-directed mutants of the bacterial photosynthetic reaction center (RC) from the 2.4.1\nand WS 231 wild-type strains of Rhodobacter sphaeroides have been crystallized and their X-ray diffraction\nanalyzed to resolutions between 3.0 and 4.0 \u00c5. The mutations can be divided into four distinct categories:\n(1) mutations altering cofactor composition that affect electron transfer and quantum yield, His M202 \u2192 Leu (M202HL), His L173 \u2192 Leu (L173HL), and Leu M214 \u2192\n His (M214LH); (2) a mutation in the\nproposed pathway of electron transfer altering electron-transfer kinetics, Tyr M210 \u2192 Phe (M210YF);\n(3) a mutation around the non-heme iron resulting in an iron-less reaction center, His M219 \u2192 Cys (M219HC); and (4) mutations around the secondary electron acceptor, a ubiquinone, affecting proton\ntransfer and quinone turnover, Glu L212 \u2192 Gin (L212EQ) and Asp L213 \u2192 Asn (L213DN). Residues\nL173 and M202 are within bonding distance of the respective magnesiums of the two bacteriochlorophylls\nof the BChl special pair, while M214 is close to the bacteriopheophytin on the active A branch of the RC.\nThe L173HL and M202HL crystal structures show that the respective bacteriochlorophylls are replaced\nwith bacteriopheophytins (i.e., loss of magnesium) without significant structural perturbations to the\nsurrounding main-chain or side-chain atoms. In the M214LH mutant, the bacteriopheophytin has been\nreplaced by a bacteriochlorophyll, and the side chain of His M214 is within ligand distance of the magnesium.\nThe M210YF, L212EQ, and L213DN mutants show no significant tertiary structure changes near the\nmutation sites. The M219HC diffraction data indicate that the overall tertiary structure of the reaction\ncenter is maintained in the absence of the non-heme iron.", "date": "1994-04-19", "date_type": "published", "publication": "Biochemistry", "volume": "33", "number": "15", "publisher": "American Chemical Society", "pagerange": "4584-4593", "id_number": "CaltechAUTHORS:20150205-141324993", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141324993", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "GM41300" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM41637" }, { "agency": "NIH", "grant_number": "GM00536" }, { "agency": "NIH", "grant_number": "GM38214/48254" }, { "agency": "European Molecular Biology Organization (EMBO)" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)" } ] }, "doi": "10.1021/bi00181a020", "resource_type": "article", "pub_year": "1994", "author_list": "Chirino, Arthur J.; Lous, Erik J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1b3ev-91846", "eprint_id": 54448, "eprint_status": "archive", "datestamp": "2023-08-20 03:52:36", "lastmod": "2023-10-20 16:28:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongsun", "name": { "family": "Kim", "given": "Jongsun" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Nitrogenase and Biological Nitrogen Fixation", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1994 American Chemical Society.\n\nReceived September 28, 1993; Revised Manuscript Received November 12, 1993.\n\nWork in the authors' lab was supported by USPHS Grant GM45162 (Fe-protein) and NSF Grant DMB 91-18689 (MoFe-protein).\n\nThe invaluable contributions of B. T. Hsu, M.M. Georgiadis, D. Woo, M.W. Day, M.K. Chan, H. Komiya, J.L. Schlessman, L. Joshua-Tor, A.J. Chirino, and M.H.B. Stowell to various phases of this project are deeply appreciated, as are numerous discussions with J.B. Howard.", "abstract": "Biological nitrogen fixation is catalyzed by the nitrogenase enzyme system which consists of\ntwo metalloproteins, the iron (Fe-) protein and the molybdenum-iron (MoFe-) protein. Together, these\nproteins mediate the ATP-dependent reduction of dinitrogen to ammonia. Recent crystallographic analyses\nof Fe-protein and MoFe-protein have revealed the polypeptide fold and the structure and organization of\nthe unusual metal centers in nitrogenase. These structure provide a molecular framework for addressing\nthe mechanism of the nitrogenase-catalyzed reaction. General features of the nitrogenase system, including\nconformational coupling of nucleotide hydrolysis, aspects of the cluster structures, and the general spatial\norganization of redox centers within the protein subunits, are relevant to a wide range of biochemical\nsystems.", "date": "1994-01-18", "date_type": "published", "publication": "Biochemistry", "volume": "33", "number": "2", "publisher": "American Chemical Society", "pagerange": "389-397", "id_number": "CaltechAUTHORS:20150205-141446723", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141446723", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "U.S. Public Health Service", "grant_number": "GM45162" }, { "agency": "NSF", "grant_number": "DMB 91-18689" } ] }, "doi": "10.1021/bi00168a001", "resource_type": "article", "pub_year": "1994", "author_list": "Kim, Jongsun and Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xxfs5-0ga20", "eprint_id": 54450, "eprint_status": "archive", "datestamp": "2023-08-20 03:21:44", "lastmod": "2023-10-20 16:28:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Dinitrogen Reduction by Nitrogenase: If N_2 Isn't Broken, It Can't be Fixed", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1993 Current Biology Ltd.\n\nThis work was supported by National Institutes of Health grant GM45162 and National Science Foundation grant DMB91-18689. The contributions of J. Kim, MM Georgiadis, BT Hsu, H Komiya, MK Chan, D Woo, JL Schlessman, MW Day, AJ Chirino, MHB Stowell and L Joshua-Tor to the crystallographic work at Caltech, along with most enjoyable discussions with JB Howard, made this review possible.", "abstract": "Nitrogenase consists of two component metalloproteins, the iron protein and molybdenum-iron protein, which together catalyze the ATP-dependent reduction of dinitrogen to ammonia during biological nitrogen fixation. With the recent crystal structure determinations of both proteins, a structural framework is now available for interpreting the mechanism of nitrogenase at the molecular level.", "date": "1993-12", "date_type": "published", "publication": "Current Opinion in Structural Biology", "volume": "3", "number": "6", "publisher": "Elsevier", "pagerange": "921-928", "id_number": "CaltechAUTHORS:20150205-141635090", "issn": "0959-440X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141635090", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NSF", "grant_number": "DMB91-18689" } ] }, "doi": "10.1016/0959-440X(93)90157-G", "resource_type": "article", "pub_year": "1993", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f0064-ss265", "eprint_id": 53969, "eprint_status": "archive", "datestamp": "2023-08-20 03:19:51", "lastmod": "2023-10-19 22:27:16", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Kyoung-Hee", "name": { "family": "Kim", "given": "Kyoung-Hee" } }, { "id": "Kwon-Byoung-Mog", "name": { "family": "Kwon", "given": "Byoung-Mog" } }, { "id": "Myers-A-G", "name": { "family": "Myers", "given": "Andrew G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystal structure of neocarzinostatin, an antitumor protein-chromophore complex", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1993 American Association for the Advancement of Science.\n\n24 June 1993; accepted 13 September 1993.\n\nWe thank L. Joshua-Tor and B. T. Hsu for their many contributions to this project, P. J. Bjorkman for discussions, and P. van Roey for providing the refined MCM coordinates. NCS powder was a generous gift of Kayaku Co., Ltd. Supported by NIH (CA47148) (A.G.M.), with partial support of the x-ray facility (GM45162) (D.C.R.) and instrumentation provided by the Beckman Institute and the Irvine Equipment fund.", "abstract": "Structures of the protein-chromophore complex and the apoprotein form of neocarzinostatin were determined at 1.8 angstrom resolution. Neocarzinostatin is composed of a labile chromophore with DNA-cleaving activity and a stabilizing protein. The chromophore displays marked nonlinearity of the triple bonds and is bound noncovalently in a pocket formed by the two protein domains. The chromophore \u03c0-face interacts with the phenyl ring edges of Phe^(52) and Phe^(78). The amino sugar and carbonate groups of the chromophore are solvent exposed, whereas the epoxide, acetylene groups, and carbon C-12, the site of nucleophilic thiol addition during chromophore activation, are unexposed. The position of the amino group of the chromophore carbohydrate relative to C-12 supports the idea that the amino group plays a role in thiol activation.", "date": "1993-11-12", "date_type": "published", "publication": "Science", "volume": "262", "number": "5136", "publisher": "American Association for the Advancement of Science", "pagerange": "1042-1046", "id_number": "CaltechAUTHORS:20150121-161817850", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150121-161817850", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Kayaku Co., Ltd" }, { "agency": "NIH", "grant_number": "CA47148" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Irvine Equipment fund" } ] }, "doi": "10.1126/science.8235619", "resource_type": "article", "pub_year": "1993", "author_list": "Kim, Kyoung-Hee; Kwon, Byoung-Mog; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/36sw5-pne08", "eprint_id": 54452, "eprint_status": "archive", "datestamp": "2023-08-22 09:36:51", "lastmod": "2023-10-20 16:29:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Wolfe-G-M", "name": { "family": "Wolfe", "given": "Gershon M." }, "orcid": "0000-0001-6586-4043" } ] }, "title": "Macromolecular Solvation Energies Derived from Small Molecule Crystal Morphology", "ispublished": "pub", "full_text_status": "restricted", "keywords": "crystal morphology; succinic acid; solvation energies", "note": "\u00a9 1993 The Protein Society.\n\nReceived June 24, 1993; Accepted July 29, 1993.\n\nWe thank D.S. Eisenberg, B. T. Hsu, and E.D. Rees for discussions.\nThis work was partially supported by NIH grants\nGM39558 and GM45162.", "abstract": "The morphology of small molecule crystals provides a model for evaluating surface solvation energies in a system with similar packing density to that observed for amino acid residues in proteins. The solvation energies associated with the transfer of methylene and carboxyl groups between vacuum and aqueous phases are estimated to be approx. +40 and -260 cal/\u00c5^2, respectively, from an analysis of the morphology of succinic acid crystals. These solvation energies predict values for contact angles in reasonable agreement with measurements determined from macroscopic monolayer surfaces. Transfer free energies between vapor and water phases for a series of carboxylic acids are also predicted reasonably well by these solvation energies, provided the surface exposure of different groups is quantitated with the molecular surface area rather than the more traditional accessible surface area. In general, molecular surfaces and molecular surface areas are seen to have important advantages for characterizing the structure and energetics of macromolecular surfaces. Crystal faces of succinic acid with the lowest surface energies in aqueous solution are characteristically smooth. Increasing surface roughness and apolarity are associated with higher surface energies, which suggests an approach for modifying the surface properties of proteins and other macromolecules.", "date": "1993-11", "date_type": "published", "publication": "Protein Science", "volume": "2", "number": "11", "publisher": "Wiley", "pagerange": "1882-1889", "id_number": "CaltechAUTHORS:20150205-141720055", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141720055", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM39558" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1002/pro.5560021110", "pmcid": "PMC2142285", "resource_type": "article", "pub_year": "1993", "author_list": "Rees, Douglas C. and Wolfe, Gershon M." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p4pd4-3nh26", "eprint_id": 54453, "eprint_status": "archive", "datestamp": "2023-08-20 03:08:35", "lastmod": "2023-10-20 16:29:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhu-Xiaotian", "name": { "family": "Zhu", "given": "Xiaotian" } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "Barbara T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural studies of the binding of the anti-ulcer drug sucrose octasulfate to acidic fibroblast growth factor", "ispublished": "pub", "full_text_status": "restricted", "keywords": "anti-ulcer drugs, fibroblast growth factors, heparin, sucrose octasulfate", "note": "\u00a9 1993 Current Biology Ltd.\n\nReceived: 24 May 1993; revised: 2 July 1993.\nAccepted: 8 July 1993.\n\nWe thank AJ Chirino for his contributions to the\ngraphics and refinement, T Arakawa and GM Fox of Amgen for providing\naFGF, and D Bar-Shalom of Bukh Meditec for the SOS sample.\nThis work was supported by in part by USPHS GM39558 and\nGM45162 (for the X-ray and computer facilities).", "abstract": "Background: The anti-ulcer drug sucrose octasulfate (SOS) binds to fibroblast growth factors (FGFs), proteins which stimulate the growth and differentiation of several cell types, including stomach epithelial cells. It is believed that SOS stabilizes FGFs against acid denaturation in the stomach, thus enhancing their ability to stimulate healing of ulcerated tissue. SOS binds to the same site on FGF as heparin and other proteoglycans, in vivo, FGF must bind to cell-surface proteoglycans or to heparin before it can interact with FGF receptors and stimulate growth. The details of this process are not understood.\n\nResults: We report the crystal structure of a 1:1 complex between acidic FGF (aFGF) and SOS at 2.7 \u00c5 resolution. SOS binds to a positively charged region of aFGF, largely composed of residues 112\u2013127, and makes contacts primarily with Lys112, Arg116, Lys118, and Arg122. This region is also important in binding heparin. The overall conformation of aFGF is not changed by binding SOS, although the positions of some side chains in the binding site shift by as much as 6 \u00c5.\n\nConclusion: The SOS-FGF crystal structure is consistent with the model that SOS stabilizes FGF by neutralizing several positively charged residues that would destabilize the native structure by electrostatic repulsion. On the basis of this structure, we provide a model for the complex of heparin with an FGF dimer. Such interactions may facilitate FGF receptor dimerization, which may be important in receptor signaling.", "date": "1993-09-15", "date_type": "published", "publication": "Structure", "volume": "1", "number": "1", "publisher": "Cell Press", "pagerange": "27-34", "id_number": "CaltechAUTHORS:20150205-141809743", "issn": "0969-2126", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141809743", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM39558" }, { "agency": "NIH", "grant_number": "GM45162" } ] }, "doi": "10.1016/0969-2126(93)90006-3", "resource_type": "article", "pub_year": "1993", "author_list": "Zhu, Xiaotian; Hsu, Barbara T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4kz77-25d78", "eprint_id": 85653, "eprint_status": "archive", "datestamp": "2023-08-20 02:57:46", "lastmod": "2024-01-14 19:35:11", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Kim-J", "name": { "family": "Kim", "given": "J." } }, { "id": "Georgiadis-M-M", "name": { "family": "Georgiadis", "given": "M. M." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Chirino-A-J", "name": { "family": "Chirino", "given": "A. J." } }, { "id": "Woo-D", "name": { "family": "Woo", "given": "D." } }, { "id": "Schlessman-J", "name": { "family": "Schlessman", "given": "J." } }, { "id": "Chan-M-K", "name": { "family": "Chan", "given": "M. K." } }, { "id": "Joshua-Tor-L", "name": { "family": "Joshua-Tor", "given": "L." } }, { "id": "Santillan-G", "name": { "family": "Santillan", "given": "G." } }, { "id": "Chakrabarti-P", "name": { "family": "Chakrabarti", "given": "P." } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "B. T." } } ] }, "title": "Crystal Structures of the Iron Protein and Molybdenum-Iron Protein of Nitrogenase", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1993 American Chemical Society. \n\nReceived March 8, 1993. Published in print 26 July 1993. \n\nStimulating discussions with J.B. Howard, J.E. Bercaw and\nH.B. Gray are gready appreciated. This work was supported by NSF DMB91-18689 and NIH GM45162. The rotation camera facility at the Stanford Synchrotron Radiation Laboratory is supported by the DOE Office of Basic Energy Sciences and the NIH Biomedical Resource Technology Program, Division of Research Resources. X-PLOR calculations wre performed on the CRAY-YMP at the San Diego Supercomputer Center, supported by NSF.", "abstract": "Three-dimensional structures of the nitrogenase iron protein and molybdenum-iron protein from Azotobacter vinelandii have been determined by x-ray crystallography. The iron protein contains a single 4Fe:4S cluster symmetrically liganded by two identical subunits. The molybdenum-iron protein is an \u03b1_2\u03b2_2 tetramer, where the homologous \u03b1 and \u03b2 subunits surround two different types of metal centers: the FeMo-cofactor and the P-cluster pair. Both centers are constructed from two bridged clusters; the FeMo-cofactor has 4Fe:3S and 1Mo:3Fe:3S cluster bridged by three non-protein ligands, while the P-cluster pair contains two 4Fe:4S clusters bridged by two cysteine ligands located at the \u03b1\u03b2 subunit interface. Docking studies between the iron protein and molybdenum iron protein suggest a possible interaction mode between these two proteins.", "date": "1993-07-26", "date_type": "published", "publisher": "American Chemical Society", "id_number": "CaltechAUTHORS:20180405-140056548", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180405-140056548", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB91-18689" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1021/bk-1993-0535.ch011", "resource_type": "book_section", "pub_year": "1993", "author_list": "Rees, D. C.; Kim, J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pp3vz-y7q71", "eprint_id": 54455, "eprint_status": "archive", "datestamp": "2023-08-20 02:57:25", "lastmod": "2023-10-20 16:29:24", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongsun", "name": { "family": "Kim", "given": "Jongsun" } }, { "id": "Woo-D", "name": { "family": "Woo", "given": "D." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "X-ray Crystal Structure of the Nitrogenase Molybdenum-Iron Protein from Clostridium pasteurianum at 3.0-\u00c5 Resolution", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1993 American Chemical Society.\n\nReceived December 7, 1992; Revised Manuscript Received March 29, 1993.\n\nThis work was supported by NSF Grant DMB 91-18689.", "abstract": "The crystal structure of the nitrogenase molybdenum-iron (MoFe) protein from Clostridium\npasteurianum (Cp1) has been determined at 3.0-\u00c5 resolution by a combination of isomorphous replacement,\nmolecular replacement, and noncrystallographic symmetry averaging. The structure of Cp1, including the\ntwo types of metal centers associated with the protein (the FeMo-cofactor and the P-cluster pair), is similar\nto that previously described for the MoFe-protein from Azotobacter vinelandii (Av1). Unique features of\nthe Cpl structure arise from the presence of an ~50-residue insertion in the \u03b1 subunit and an ~50-residue\ndeletion in the \u03b2 subunit. As a consequence, the FeMo-cofactor is more buried in Cp1 than in Av1, since\nthe insertion is located on the surface above the FeMo-cofactor. The location of this insertion near the\nputative nitrogenase iron protein binding site provides a structural basis for the observation that the nitrogenase\nproteins from C. pasteurianum have low activity with complementary nitrogenase proteins isolated from\nother organisms. Mechanistic implications of the Cp1 structure for substrate entry /product release,\nsubstrate binding to the FeMo-cofactor, and electron- and proton-transfer reactions of nitrogenase are\ndiscussed.", "date": "1993-07-20", "date_type": "published", "publication": "Biochemistry", "volume": "32", "number": "28", "publisher": "American Chemical Society", "pagerange": "7104-7115", "id_number": "CaltechAUTHORS:20150205-142032405", "issn": "0006-2960", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-142032405", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB 91-18689" } ] }, "doi": "10.1021/bi00079a006", "resource_type": "article", "pub_year": "1993", "author_list": "Kim, Jongsun; Woo, D.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/8wdhq-dba68", "eprint_id": 54449, "eprint_status": "archive", "datestamp": "2023-08-20 02:54:03", "lastmod": "2023-10-20 16:28:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Arakawa-Tsutomu", "name": { "family": "Arakawa", "given": "Tsutomu" } }, { "id": "Horan-T-P", "name": { "family": "Horan", "given": "Thomas P." } }, { "id": "Narhi-L-O", "name": { "family": "Narhi", "given": "Linda O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Schiffer-Susan-G", "name": { "family": "Schiffer", "given": "Susan G." } }, { "id": "Holst-P-L", "name": { "family": "Holst", "given": "Paige L." } }, { "id": "Prestrelski-S-J", "name": { "family": "Prestrelski", "given": "Steven J." } }, { "id": "Tsai-Larry-B", "name": { "family": "Tsai", "given": "Larry B." } }, { "id": "Fox-Gary-M", "name": { "family": "Fox", "given": "Gary M." } } ] }, "title": "Production and Characterization of an Analog of Acidic Fibroblast Growth Factor with Enhanced Stability and Biological Activity", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1993 Oxford University Press.\n\nReceived on October 23, 1992; revised on March 16, 1993; accepted on March 30, 1993.", "abstract": "We have used recombinant DNA methods to produce two forms of bovine acidic fibroblast growth factor (aFGF), one with alanine substituted for the cysteine at position 47 and the other with the Ala47 change plus the substitution of glycine for the naturally occurring histidine at position 93. Both forms were expressed at high levels in Eschtrichia coli and purified to near homogeneity by solubilization of the inclusion bodies containing the aFGF, ion exchange chromatography, refolding of the protein and hydrophobic interaction chromatography. Circular dichroic and infrared spectra suggested that the proteins are similar in secondary and tertsiary structures and contain little or no \u03b1-helical conformations. Hydrophobic interaction chromatography showed that aFGF C47A/H93G is slightly more hydrophobic than the aFGF C47A form, suggesting that residue 93 is exposed to the solvent. Half-maximal activity in an in vitro bioassay system was reached at a 10- to 20-fold lower dose for the aFGF C47A/H93G form than for the aFGF C47A form, suggesting that alteration of this residue has an effect on the region responsible for receptor binding. Addition of 50 \u03bcg/ml heparin enhanced the in vitro activity of the aFGFs, reducing the half-maximal dose to approximately 100 pg/ml for both forms, comparable to that observed previously for basic FGF with or without heparin in this assay system.", "date": "1993-07", "date_type": "published", "publication": "Protein Engineering", "volume": "6", "number": "5", "publisher": "Oxford University Press", "pagerange": "541-546", "id_number": "CaltechAUTHORS:20150205-141530315", "issn": "0269-2139", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141530315", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1093/protein/6.5.541", "resource_type": "article", "pub_year": "1993", "author_list": "Arakawa, Tsutomu; Horan, Thomas P.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/x5j6x-20q84", "eprint_id": 53121, "eprint_status": "archive", "datestamp": "2023-08-20 02:42:57", "lastmod": "2023-10-19 14:33:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chan-Michael-K", "name": { "family": "Chan", "given": "Michael K." } }, { "id": "Kim-Jongsun", "name": { "family": "Kim", "given": "Jongsun" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Nitrogenase FeMo-Cofactor and P-Cluster Pair: 2.2 \u00c5 Resolution Structures", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1993 American Association for the Advancement of Science.\n\n13 October 1992; Accepted 28 January 1993.\n\nD. Malerba are appreciated. Research supported by NSF grant DMB 91-18689. M.K.C. is the recipient of NIH fellowship 1 F32 GM1 5006. The rotation camera facility at the Stanford Synchrotron Radiation Laboratory is supported by the Department of Energy, Office of Basic Energy Sciences, and\nthe NIH Biomedical Resource Technology Program, Division of Research Resources. The program X-PLOR was run on the CRAY-YMP at the San Diego Supercomputer Center, supported by NSF.", "abstract": "Structures recently proposed for the FeMo-cofactor and P-cluster pair of the nitrogenase molybdenum-iron (MoFe)-protein from Azotobacter vinelandii have been crystallographically verified at 2.2 angstrom resolution. Significantly, no hexacoordinate sulfur atoms are observed in either type of metal center. Consequently, the six bridged iron atoms in the FeMo-cofactor are trigonally coordinated by nonprotein ligands, although there may be some iron-iron bonding interactions that could provide a fourth coordination interaction for these sites. Two of the cluster sulfurs in the P-cluster pair are very close together (approximately 2.1 angstroms), indicating that they form a disulfide bond. These findings indicate that a cavity exists in the interior of the FeMo-cofactor that could be involved in substrate binding and suggest that redox reactions at the P-cluster pair may be linked to transitions of two cluster-bound sulfurs between disulfide and sulfide oxidation states.", "date": "1993-05-07", "date_type": "published", "publication": "Science", "volume": "260", "number": "5109", "publisher": "American Association for the Advancement of Science", "pagerange": "792-794", "id_number": "CaltechAUTHORS:20141222-155310099", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141222-155310099", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB 91-18689" }, { "agency": "NIH", "grant_number": "1F32 GM15006" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1126/science.8484118", "resource_type": "article", "pub_year": "1993", "author_list": "Chan, Michael K.; Kim, Jongsun; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/d6q5p-khq76", "eprint_id": 54456, "eprint_status": "archive", "datestamp": "2023-08-20 02:31:46", "lastmod": "2023-10-20 16:29:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Stowell-M-H-B", "name": { "family": "Stowell", "given": "Michael H. B." } }, { "id": "Larsen-R-W", "name": { "family": "Larsen", "given": "Randy W." } }, { "id": "Winkler-J-R", "name": { "family": "Winkler", "given": "Jay R." }, "orcid": "0000-0002-4453-9716" }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Chan-S-I", "name": { "family": "Chan", "given": "Sunney I." }, "orcid": "0000-0002-5348-2723" } ] }, "title": "Transient electron-transfer studies on the two-subunit cytochrome c oxidase from Paracoccus denitrificans", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1993 American Chemical Society.\n\nReceived: November 23, 1992.\n\nContribution No. 8722 from the Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA. This work was supported by Grant GM22432 from the National Institute of General Medical Science, U.S.P.H.S. Portions described at the ASBMB/Biophysical Society Joint Meeting. FASEB J. 1992, 6, A284.\n\nWe thank Siegfried M. Musser and Dr. Theodore J. DiMagno for helpful discussions and critically reviewing this manuscript. We also thank Dr. Thomas Harrold and Larry Tudor for expert assistance in the growth of P. denitrificans.", "abstract": "Intermolecular electron transfer between c-type cytochromes (equine cytochrome c_(550), P. denitrifcans c_(550), and\nP. denitrificans detergent solubilized membrane-associated c_(552)) and the two-subunit cytochrome c oxidase\nfrom P. denitrificans has been studied using a photoinitiated uroporphyrin/NADH reduction system. In the\npresence of cytochrome c oxidase, the oxidation of transiently produced soluble ferrocytochrome c_(550)'s was\nbiphasic with a fast phase k_(obs) between 80 and 90 s^(-1). The simultaneous reduction of cytochrome a occurred\nwith a k(obs) of 50 s^(-1), suggesting that cytochrome a is not the immediate electron acceptor for these soluble\ncytochromes. In contrast, the membrane-associated cytochrome c_(552) was not capable of transferring electrons\nto cytochrome c oxidase, either transiently or under steady-state conditions. It is concluded that the soluble\nand membrane-associated cytochrome c's utilize separate electron-transfer pathways into P. denitrifcans\ncytochrome c oxidase.", "date": "1993-03-25", "date_type": "published", "publication": "Journal of Physical Chemistry", "volume": "97", "number": "12", "publisher": "American Chemical Society", "pagerange": "3054-3057", "id_number": "CaltechAUTHORS:20150205-142230754", "issn": "0022-3654", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-142230754", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM22432" }, { "agency": "National Institute of General Medical Sciences" } ] }, "other_numbering_system": { "items": [ { "id": "8722", "name": "Caltech Division of Chemistry and Chemical Engineering" } ] }, "doi": "10.1021/j100114a036", "resource_type": "article", "pub_year": "1993", "author_list": "Stowell, Michael H. B.; Larsen, Randy W.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zycda-4c027", "eprint_id": 54454, "eprint_status": "archive", "datestamp": "2023-08-20 02:07:34", "lastmod": "2023-10-20 16:29:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Chan-M-K", "name": { "family": "Chan", "given": "Michael K." } }, { "id": "Kim-Jongsun", "name": { "family": "Kim", "given": "Jongsun" } } ] }, "title": "Structure and Function of Nitrogenase", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1994 Academic Press Inc. Published by Elsevier Ltd.\n\nThe contributions of M. Georgiadis, H. Komiya, D. Woo, B. T. Hsu, M. Day, G. Santillan,\nM. Stowell, J. Schlessman, and L. Joshua-Tor to this work are gratefully acknowledged,\nas are discussions with H. B. Gray and J. E. Bercaw. As always, the insights of J. B.\nHoward have been most illuminating. Structural studies of the MoFe-protein conducted\nby the author were supported by NSF CMB 91-18689, whereas the Fe-protein work was\nsupported by NIH GM45162. M. K. Chan was supported by NIH Fellowship 1F32\nGM15006.", "abstract": "This chapter discusses the structures of the metal centers and polypeptide chains of the nitrogenase proteins based on the crystallographic structures of both the Fe-protein and the MoFe protein that have been determined at Caltech. The discussion is presented in the context of the nitrogenase protein structures. The two nitrogenase proteins, Fe-protein and MoFe-protein, are composed of a total of three different types of subunits and contain three different types of metal centers. The properties of the nitrogenase proteins have been discussed in the chapter. To distinguish the two nitrogenase proteins, isolated from different bacterial sources, the MoFe-protein and Fe-protein are designated as components \"1\" and \"2,\" respectively, preceded by a two-letter abbreviation of the source species and genus\u2014that is, Av1 is MoFe-protein isolated from Azotobacter vinelandii and Cp2 is Fe-protein isolated from Clostridium pasteurianum, etc. In addition to the mechanistic role in the nitrogenase enzymatic function, Fe-protein also participates at several stages in the biosynthesis of the nitrogenase proteins. The chapter explains the nitrogenase mechanism from the viewpoint of an electron traveling through the system. The Haber\u2013Bosch process utilizes an iron catalyst to accelerate the rate of ammonia formation from dinitrogen and hydrogen.", "date": "1993", "date_type": "published", "publication": "Advances in Inorganic Chemistry", "volume": "40", "publisher": "Elsevier", "pagerange": "89-119", "id_number": "CaltechAUTHORS:20150205-141930383", "issn": "0898-8838", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-141930383", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CMB 91-18689" }, { "agency": "NIH", "grant_number": "GM45162" }, { "agency": "NIH", "grant_number": "1F32 GM15006" } ] }, "doi": "10.1016/S0898-8838(08)60182-8", "resource_type": "article", "pub_year": "1993", "author_list": "Rees, Douglas C.; Chan, Michael K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7t4dk-c0v38", "eprint_id": 54210, "eprint_status": "archive", "datestamp": "2023-08-20 01:59:19", "lastmod": "2023-10-19 23:45:45", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongsun", "name": { "family": "Kim", "given": "Jongsun" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystallographic Structure and Functional Implications of the Nitrogenase Molybdenum-Iron Protein from Azotobacter vinelandii", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1992 Nature Publishing Group.\n\nReceived 17 September; accepted 24 November 1992.\n\nWe thank J. B. Howard, A. J. Chirino, B. T. Hsu, M. K. Chan, H. Kamiya, D. Woo,\nG. Santillan and D. Malerba for contributions to this project. This work was supported by the NSF, with instrumentation funded in part by the Beckman Institute and the Joseph Irvine Equipment fund. X-PLOR calculations were done on the CRAY-YMP at the San Diego Supercomputer Center, supported by the NSF. Coordinates will be deposited in the Brookhaven Protein Data Bank, and are available by E-mail (REES@CITRAY.CALTECH.EDU).", "abstract": "The crystal structure of the nitrogenase molybdenum\u2013iron protein from Azotobacter vinelandii has been determined at 2.7 \u00c5 resolution. The \u03b1- and \u03b2-subunits in this \u03b1_2\u03b2_2 tetramer have similar polypeptide folds. The FeMo-cofactor is completely encompassed by the \u03b1-subunit, whereas the P-cluster pair occurs at the interface between \u03b1- and \u03b2-subunits. Structural similarities are apparent between nitrogenase and other electron transfer systems, including hydrogenases and the photosynthetic reaction centre.", "date": "1992-12-10", "date_type": "published", "publication": "Nature", "volume": "360", "number": "6404", "publisher": "Nature Publishing Group", "pagerange": "553-560", "id_number": "CaltechAUTHORS:20150128-164438686", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150128-164438686", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Joseph Irvine Equipment Fund" } ] }, "doi": "10.1038/360553a0", "resource_type": "article", "pub_year": "1992", "author_list": "Kim, Jongsun and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pf459-s1075", "eprint_id": 54535, "eprint_status": "archive", "datestamp": "2023-08-22 09:03:40", "lastmod": "2023-10-20 16:54:58", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Blake-P-R", "name": { "family": "Blake", "given": "Paul R." } }, { "id": "Day-M-W", "name": { "family": "Day", "given": "Michael W." } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "Barbara T." } }, { "id": "Joshua-Tor-L", "name": { "family": "Joshua-Tor", "given": "Leemor" } }, { "id": "Park-Jae-Bum", "name": { "family": "Park", "given": "Jae-Bum" } }, { "id": "Hare-D-R", "name": { "family": "Hare", "given": "Dennis R." } }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Summers-M-F", "name": { "family": "Summers", "given": "Michael F." } } ] }, "title": "Comparison of the X-ray Structure of Native Rubredoxin from Pyrococcus furiosus with the NMR Structure of the Zinc-Substituted Protein", "ispublished": "pub", "full_text_status": "public", "keywords": "distance geometry; hyperthermophile; iron-sulfur protein; NMR structure; protein structure; rubredoxin; X-ray structure; zinc substitution", "note": "\u00a9 1992 The Protein Society.\n\nReceived April 29, 1992; Revised manuscript received June 19, 1992.\n\nPublished - 55_blake_1992.pdf
", "abstract": "The three-dimensional X-ray structures of the oxidized and reduced forms of rubredoxin from Pyrococcus furiosus, determined at -161\u00b0C, and the NMR structure of the zinc-substituted protein, determined in solution at 45\u00b0C, are compared. The NMR and X-ray structures, which were determined independently, are very similar and lead to similar conclusions regarding the interactions that confer hyperthermostability.", "date": "1992-11", "date_type": "published", "publication": "Protein Science", "volume": "1", "number": "11", "publisher": "Cambridge University Press", "pagerange": "1522-1525", "id_number": "CaltechAUTHORS:20150209-101846134", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-101846134", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1002/pro.5560011113", "pmcid": "PMC2142123", "primary_object": { "basename": "55_blake_1992.pdf", "url": "https://authors.library.caltech.edu/records/pf459-s1075/files/55_blake_1992.pdf" }, "resource_type": "article", "pub_year": "1992", "author_list": "Blake, Paul R.; Day, Michael W.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kh13k-19546", "eprint_id": 54536, "eprint_status": "archive", "datestamp": "2023-08-22 09:03:45", "lastmod": "2023-10-20 16:55:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Day-M-W", "name": { "family": "Day", "given": "Michael W." } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "Barbara T." } }, { "id": "Joshua-Tor-L", "name": { "family": "Joshua-Tor", "given": "Leemor" } }, { "id": "Park-Jae-Bum", "name": { "family": "Park", "given": "Jae-Bum" } }, { "id": "Zhou-Zhi-Hao", "name": { "family": "Zhou", "given": "Zhi Hao" } }, { "id": "Adams-M-W-W", "name": { "family": "Adams", "given": "Michael W. W." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "X-ray Crystal Structures of the Oxidized and Reduced forms of the Rubredoxin from the Marine Hyperthermophilic Archaebacterium Pyrococcus furiosus", "ispublished": "pub", "full_text_status": "public", "keywords": "electron transfer proteins; protein stability; protein structure; rubredoxin; thermostability", "note": "\u00a9 1992 The Protein Society.\n\nReceived April 29, 1992; Revised manuscript received June 9, 1992.\n\nWe thank A.J. Chirino for his advice and assistance throughout the course of this research. This work was supported by grants from the National Science Foundation DMB-9118689 (D.C.R), and BCS-9011583 (M.W.W.A.), the Office of Naval Research N00014-90-J-1894 (M.W.W.A.), and by a National Science Foundation Training Group Award to the Center for Metalloenzyme Studies of the University of Georgia DIR-9014281. We also acknowledge the Department of Education (M.W.D.) and a Weizmann postdoctoral fellowship (L.J.) for support.\n\nPublished - 54_day_1992.pdf
", "abstract": "The structures of the oxidized and reduced forms of the rubredoxin from the archaebacterium, Pyrococcus furiosus, an organism that grows optimally at 100 \u00b0C, have been determined by X-ray crystallography to a resolution of 1.8 \u00e5. Crystals of this rubredoxin grow in space group P2_12_12_1 with room temperature cell dimensions a = 34.6 \u00e5, b = 35.5 \u00e5, and c = 44.4 \u00e5. Initial phases were determined by the method of molecular replacement using the oxidized form of the rubredoxin from the mesophilic eubacterium, Clostridium pasteurianum, as a starting model. The oxidized and reduced models of P. furiosus rubredoxin each contain 414 nonhydrogen protein atoms comprising 53 residues. The model of the oxidized form contains 61 solvent H_2O oxygen atoms and has been refined with X-PLOR and TNT to a final R = 0.178 with root mean square (rms) deviations from ideality in bond distances and bond angles of 0.014 \u00e5 and 2.06\u00b0, respectively. The model of the reduced form contains 37 solvent H2O oxygen atoms and has been refined to R = 0.193 with rms deviations from ideality in bond lengths of 0.012 \u00e5 and in bond angles of 1.95\u00b0. The overall structure of P. furiosus rubredoxin is similar to the structures of mesophilic rubredoxins, with the exception of a more extensive hydrogen-bonding network in the \u03b2-sheet region and multiple electrostatic interactions (salt bridge, hydrogen bonds) of the Glu 14 side chain with groups on three other residues (the amino-terminal nitrogen of Ala 1; the indole nitrogen of Trp 3; and the amide nitrogen group of Phe 29). The influence of these and other features upon the thermostability of the P. furiosus protein is discussed.", "date": "1992-11", "date_type": "published", "publication": "Protein Science", "volume": "1", "number": "11", "publisher": "Cambridge University Press", "pagerange": "1494-1507", "id_number": "CaltechAUTHORS:20150209-101936300", "issn": "0961-8368", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-101936300", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB-9118689" }, { "agency": "NSF", "grant_number": "BCS-9011583" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-90-J-1894" }, { "agency": "NSF", "grant_number": "DIR-9014281" }, { "agency": "Department of Education" }, { "agency": "Weizmann Postdoctoral Fellowship (Caltech)" } ] }, "doi": "10.1002/pro.5560011111", "pmcid": "PMC2142115", "primary_object": { "basename": "54_day_1992.pdf", "url": "https://authors.library.caltech.edu/records/kh13k-19546/files/54_day_1992.pdf" }, "resource_type": "article", "pub_year": "1992", "author_list": "Day, Michael W.; Hsu, Barbara T.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yd551-vcc53", "eprint_id": 54005, "eprint_status": "archive", "datestamp": "2023-08-20 01:44:14", "lastmod": "2023-10-19 22:29:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Georgiadis-M-M", "name": { "family": "Georgiadis", "given": "M. M." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Chakrabarti-P", "name": { "family": "Chakrabarti", "given": "P." } }, { "id": "Woo-D", "name": { "family": "Woo", "given": "D." } }, { "id": "Kornuc-J-J", "name": { "family": "Kornuc", "given": "J. J." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Crystallographic structure of the nitrogenase iron protein from Azotobacter vinelandii", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1992 American Association for the Advancement of Science.\n\n19 June 1992; Accepted 18 August 1992.\n\nThis work was initiated in the laboratory of J. B. Howard, whose advice and encouragement was significant at all stages of the project. The contributions of B. T. Hsu, A. J. Chirino, L. Joshua-Tor, J. L. Schlessman, D. E. Malerba and the Caltech Structural Biology Group, D. S. Eisenberg and the UCLA Structural Biology Group, D. H. Burke, L. C.\nDavis, H. Hope, and S.-H. Kim are gratefully appreciated.\nC. D. Stout suggested the use of thiomalates as heavy atom derivatives, and T. Schaak provided the myochrisine. The rotation camera facility at the Stanford Synchrotron Radiation Laboratory is supported by the Department of Energy, Office of Basic Energy Sciences, and the National\n-Institutes of Health Biomedical Resource Technology\nProgram, Division of Research Resources. Coordinates will be deposited in the Brookhaven Protein Data Bank, and are available by E-mail (REES@CITRAY.CALTECH.EDU). Supported by\nUSPHS grant GM45162 and an NSF PYI award, with instrumentation funded in part by the Beckman Institute and the Joseph Irvine Equipment Fund.", "abstract": "The nitrogenase enzyme system catalyzes the ATP (adenosine triphosphate)-dependent reduction of dinitrogen to ammonia during the process of nitrogen fixation. Nitrogenase consists of two proteins: the iron (Fe)-protein, which couples hydrolysis of ATP to electron transfer, and the molybdenum-iron (MoFe)-protein, which contains the dinitrogen binding site. In order to address the role of ATP in nitrogen fixation, the crystal structure of the nitrogenase Fe-protein from Azotobacter vinelandii has been determined at 2.9 angstrom (A) resolution. Fe-protein is a dimer of two identical subunits that coordinate a single 4Fe:4S cluster. Each subunit folds as a single alpha/beta type domain, which together symmetrically ligate the surface exposed 4Fe:4S cluster through two cysteines from each subunit. A single bound ADP (adenosine diphosphate) molecule is located in the interface region between the two subunits. Because the phosphate groups of this nucleotide are approximately 20 A from the 4Fe:4S cluster, it is unlikely that ATP hydrolysis and electron transfer are directly coupled. Instead, it appears that interactions between the nucleotide and cluster sites must be indirectly coupled by allosteric changes occurring at the subunit interface. The coupling between protein conformation and nucleotide hydrolysis in Fe-protein exhibits general similarities to the H-Ras p21 and recA proteins that have been recently characterized structurally. The Fe-protein structure may be relevant to the functioning of other biochemical energy-transducing systems containing two nucleotide-binding sites, including membrane transport proteins.", "date": "1992-09-18", "date_type": "published", "publication": "Science", "volume": "257", "number": "5077", "publisher": "American Association for the Advancement of Science", "pagerange": "1653-1659", "id_number": "CaltechAUTHORS:20150122-152823969", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150122-152823969", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)" }, { "agency": "NIH Biomedical Technology Resource Program" }, { "agency": "United States Public Health Service (USPHS)", "grant_number": "GM45162" }, { "agency": "NSF" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Joseph Irvine Equipment Fund" } ] }, "doi": "10.1126/science.1529353", "resource_type": "article", "pub_year": "1992", "author_list": "Georgiadis, M. M.; Komiya, H.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/9xn3p-ce928", "eprint_id": 54003, "eprint_status": "archive", "datestamp": "2023-08-20 01:44:07", "lastmod": "2023-10-19 22:29:24", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongsun", "name": { "family": "Kim", "given": "Jongsun" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structural models for the metal centers in the nitrogenase molybdenum-iron protein", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1992 American Association for the Advancement of Science.\n\n19 June 1992; Accepted 18 August 1992.\n\nDiscussions with J. B. Howard, J. E. Bercaw, and H. B. Gray and the assistance of M. M. Georgiadis, B. T. Hsu, D. Woo, A. J. Chirino, H. Komiya, D. Malerba, and M. K. Chan are gratefully appreciated. Supported by NSF grant DMB91-18689,\nwith instrumentation funded in part by the Beckman Institute and the Joseph Irvine Equipment fund.", "abstract": "Structural models for the nitrogenase FeMo-cofactor and P-clusters are proposed based on crystallographic analysis of the nitrogenase molybdenum-iron (MoFe)-protein from Azotobacter vinelandii at 2.7 angstrom resolution. Each center consists of two bridged clusters; the FeMo-cofactor has 4Fe:3S and 1Mo:3Fe:3S clusters bridged by three non-protein ligands, and the P-clusters contain two 4Fe:4S clusters bridged by two cysteine thiol ligands. Six of the seven Fe sites in the FeMo-cofactor appear to have trigonal coordination geometry, including one ligand provided by a bridging group. The remaining Fe site has tetrahedral geometry and is liganded to the side chain of Cys ^(\u03b1 275). The Mo site exhibits approximate octahedral coordination geometry and is liganded by three sulfurs in the cofactor, two oxygens from homocitrate, and the imidazole side chain of His^(\u03b1 442). The P-clusters are liganded by six cysteine thiol groups, two which bridge the two clusters, \u03b188 and \u03b295, and four which singly coordinate the remaining Fe sites, \u03b162, \u03b1154, \u03b270, and \u03b2153. The side chain of Ser^(\u03b2188) may also coordinate one iron. The polypeptide folds of the homologous \u03b1 and \u03b2 subunits surrounding the P-clusters are approximately related by a twofold rotation that may be utilized in the binding interactions between the MoFe-protein and the nitrogenase Fe-protein. Neither the FeMo-cofactor nor the P-clusters are exposed to the surface, suggesting that substrate entry, electron transfer, and product release must involve a carefully regulated sequence of interactions between the MoFe-protein and Fe-protein of nitrogenase.", "date": "1992-09-18", "date_type": "published", "publication": "Science", "volume": "257", "number": "5077", "publisher": "American Association for the Advancement of Science", "pagerange": "1677-1682", "id_number": "CaltechAUTHORS:20150122-144354973", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150122-144354973", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMB91-18689" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Joseph Irvine Equipment Fund" } ] }, "doi": "10.1126/science.1529354", "resource_type": "article", "pub_year": "1992", "author_list": "Kim, Jongsun and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/a904a-wq245", "eprint_id": 54457, "eprint_status": "archive", "datestamp": "2023-08-20 00:33:59", "lastmod": "2023-10-20 16:29:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Krantzman-K-D", "name": { "family": "Krantzman", "given": "Kristin D." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Farrelly-D", "name": { "family": "Farrelly", "given": "David" } } ] }, "title": "Computational Study of the Imaging of a Molecular Crystal with the Atomic Force Microscope", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1991 American Chemical Society.\n\nReceived: August 12, 1991.\n\nSupport from NSF, NIH, and DARPA is\ngratefully acknowledged. We thank John Milligan for assistance\nwith the graphics.", "abstract": "Atomic force microscopy (AFM) has the capacity to probe the\nsurface topography of a variety of materials with atomic scale\nresolution.Unlike scanning tunneling microscopy AFM does\nnot depend on the sample being an electrical conductor and\ntherefore provides an ideal way to image the surfaces of nonconducting\nmolecular crystals. Many studies have focused on\ncharacterizing the surfaces of metals or semiconductor crystals.\nAn alternative and potentially important application of AFM is\nto the characterization of the surfaces of biochemical crystals,\nwith a view to mapping out active sites in proteins. While AFM\nhas been able to resolve the surface structure of crystals with\natomic scale resolution, an important issue is the unique identification\nof individual surface atoms; for example, to use AFM\nto determine which cleavage plane of a molecular crystal is exposed.\nThis letter reports a numerical simulation of a recent AFM\nstudy of the {100} surface of a DL-leucine crystal performed by\nHansma and co-workers using a shattered diamond tip.", "date": "1991-11-14", "date_type": "published", "publication": "Journal of Physical Chemistry", "volume": "95", "number": "23", "publisher": "American Chemical Society", "pagerange": "9039-9042", "id_number": "CaltechAUTHORS:20150205-142330668", "issn": "0022-3654", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-142330668", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF" }, { "agency": "NIH" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" } ] }, "doi": "10.1021/j100176a006", "resource_type": "article", "pub_year": "1991", "author_list": "Krantzman, Kristin D.; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ff17k-1xd36", "eprint_id": 52453, "eprint_status": "archive", "datestamp": "2023-08-19 23:41:14", "lastmod": "2023-10-18 19:53:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhu-X", "name": { "family": "Zhu", "given": "X." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Chirino-A", "name": { "family": "Chirino", "given": "A." } }, { "id": "Faham-S", "name": { "family": "Faham", "given": "S." } }, { "id": "Fox-G-M", "name": { "family": "Fox", "given": "G. M." } }, { "id": "Arakawa-T", "name": { "family": "Arakawa", "given": "T." } }, { "id": "Hsu-B-T", "name": { "family": "Hsu", "given": "B. T." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Three-Dimensional Structures of Acidic and Basic Fibroblast Growth Factors", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1991 American Association for the Advancement of Science.\n\nReceived 19 September 1990; accepted 21 November 1990.\n\nSupported by the Beckman Institute and the Joseph Irvine Equipment Fund. D.C.R. is an A. P. Sloan Research Fellow. Coordinates will be deposited in the Brookhaven Protein Data Bank after refinement. Current coordinates may be obtained by sending a tape to D.C.R. or by Bitnet (REES@CITRAY).", "abstract": "Members of the fibroblast growth factor (FGF) family of proteins stimulate the proliferation and differentiation of a variety of cell types through receptor-mediated pathways. The three-dimensional structures of two members of this family, bovine acidic FGF and human basic FGF, have been crystallographically determined. These structures contain 12 antiparallel \u03b2 strands organized into a folding pattern with approximate threefold internal symmetry. Topologically equivalent folds have been previously observed for soybean trypsin inhibitor and interleukins-1\u03b2 and -1\u03b1. The locations of sequences implicated in receptor and heparin binding by FGF are presented. These sites include beta-sheet strand 10, which is adjacent to the site of an extended sequence insertion in several oncogene proteins of the FGF family, and which shows sequence conservation among the FGF family and interleukin-1\u03b2.", "date": "1991-01-04", "date_type": "published", "publication": "Science", "volume": "251", "number": "4989", "publisher": "American Association for the Advancement of Science", "pagerange": "90-93", "id_number": "CaltechAUTHORS:20141208-084711342", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141208-084711342", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Beckman Institute" }, { "agency": "Joseph Irvine Equipment Fund" } ] }, "doi": "10.1126/science.1702556", "resource_type": "article", "pub_year": "1991", "author_list": "Zhu, X.; Komiya, H.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p1h95-ymh21", "eprint_id": 54540, "eprint_status": "archive", "datestamp": "2023-08-19 23:14:02", "lastmod": "2023-10-20 19:04:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "An Envelope-based Approach for Direct Phase Determination of Macromolecular Structures", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1990 International Union of Crystallography.\n\nReceived 14 December 1989; accepted 12 June 1990.\n\nWe thank B. T. Hsu, R. E. Marsh, V. Schomaker, J. N. Franklin, T. O. Yeates and D. E. Malerba for discussions and programs. This work was supported by grants from the NIH, NSF and the Joseph Irvine Equipment Fund. DCR is an A. P. Sloan Research Fellow.\n\nPublished - 48_rees_1990.pdf
", "abstract": "An initial electron density distribution for a crystal structure may be directly derived from observed diffraction data by maximizing the product of the observed and calculated Patterson functions with respect to the electron density values within an envelope. This maximization problem may be formulated as an eigenvalue equation, in which potential electron density distributions are obtained as eigendensities (eigenvectors) of a symmetric matrix. Elements of this matrix depend only on the indices and intensities of the observed reflections, and on the coordinates of grid points inside the envelope. Eigendensities are calculated for a set of small envelopes (enclosing about 20% of the molecular volume) covering a unique region of the unit cell whose points are unrelated by space-group operations, origin shifts or changes in enantiomorph. On the basis of correlation coefficients between the observed and calculated values for both the Patterson function and structure factor amplitudes, a small set of eigendensities are selected for combination into a final electron density distribution. This electron density distribution may be Fourier transformed to yield calculated structure factors. Test calculations on lysozyme indicate that phase errors of less than 60\u00b0 may be obtained for strong low-resolution reflections by this procedure. An extension of this approach to handle crystal structures containing non-crystallographic symmetry is described.", "date": "1990-11", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "46", "number": "11", "publisher": "International Union of Crystallography", "pagerange": "915-922", "id_number": "CaltechAUTHORS:20150209-102351401", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-102351401", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Joseph Irvine Equipment Fund" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "doi": "10.1107/S0108767390006705", "primary_object": { "basename": "48_rees_1990.pdf", "url": "https://authors.library.caltech.edu/records/p1h95-ymh21/files/48_rees_1990.pdf" }, "resource_type": "article", "pub_year": "1990", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hha6y-dgc71", "eprint_id": 54387, "eprint_status": "archive", "datestamp": "2023-08-19 21:49:56", "lastmod": "2023-10-20 16:23:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "DeAntonion-L", "name": { "family": "DeAntonio", "given": "L." } }, { "id": "Eisenberg-D", "name": { "family": "Eisenberg", "given": "D." } } ] }, "title": "Hydrophobic organization of membrane proteins", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1989 American Association for the Advancement of Science.\n\n3 March 1989, accepted 2 June 1989.\n\nWe thank J. P. Allen and G. Feher for helpful discussions. Supported by NIH grants GM31299 and GM39558. D.G.R. is an A. P. Sloan research fellow. Programs and sequence alignments used in this work are available from D.G.R.\n\nPublished - 1704082.pdf
", "abstract": "Membrane-exposed residues are more hydrophobic than buried interior residues in the transmembrane regions of the photosynthetic reaction center from Rhodobacter sphaeroides. This hydrophobic organization is opposite to that of water-soluble proteins. The relative polarities of interior and surface residues of membrane and water soluble proteins are not simply reversed, however. The hydrophobicities of interior residues of both membrane and water-soluble proteins are comparable, whereas the bilayer-exposed residues of membrane proteins are more hydrophobic than the interior residues, and the aqueous-exposed residues of water-soluble proteins are more hydrophilic than the interior residues. A method of sequence analysis is described, based on the periodicity of residue replacement in homologous sequences, that extends conclusions derived from the known atomic structure of the reaction center to the more extensive database of putative transmembrane helical sequences.", "date": "1989-08-04", "date_type": "published", "publication": "Science", "volume": "245", "number": "4917", "publisher": "American Association for the Advancement of Science", "pagerange": "510-513", "id_number": "CaltechAUTHORS:20150204-145844789", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150204-145844789", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM31299" }, { "agency": "NIH", "grant_number": "GM39558" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "doi": "10.1126/science.2667138", "primary_object": { "basename": "1704082.pdf", "url": "https://authors.library.caltech.edu/records/hha6y-dgc71/files/1704082.pdf" }, "resource_type": "article", "pub_year": "1989", "author_list": "Rees, D. C.; DeAntonio, L.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/g718a-x8204", "eprint_id": 631, "eprint_status": "archive", "datestamp": "2023-08-22 06:25:50", "lastmod": "2023-10-13 21:54:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } } ] }, "title": "The Bacterial Photosynthetic Reaction Center as a Model for Membrane Proteins", "ispublished": "pub", "full_text_status": "public", "note": "\"Reprinted, with permission, from the Annual Review of Biochemistry, Volume 58 copyright 1989 by Annual Reviews, www.annualreviews.org\" \n\nThe authors thank D. Eisenberg, L. DeAntonio, A. Chirino, J. Deisenhofer, W. DeGrado, and D. C. Wiley for discussions and comments. Research in the laboratories of the authors has been supported by grants from NIH and NSF. DCR is an A. P. Sloan research fellow.", "abstract": "Membrane proteins participate in many fundamental cellular processes. Until recently, an understanding of the function and properties of membrane proteins was hampered by an absence of structural information at the atomic level. A landmark achievement toward understanding the structure of membrane proteins was the crystallization (1) and structure determination (2-5) the photosynthetic reaction center (RC) from the purple bacteria Rhodopseudomonas viridis, followed by that of the RC from Rhodobacter sphaeroides (6-17). The RC is an integral membrane protein-pigment complex, which carries out the initial steps of photosynthesis (reviewed in 18). RCs from the purple bacteria Rps. viridis and Rb. sphaeroides are composed of three membrane-associated protein subunits (designated L, M, and H), and the following cofactors: four bacteriochlorophylls (Bchl or B), two bacteriopheophytins (Bphe or [phi]), two quinones, and a nonheme iron. The cofactors are organized into two symmetrical branches that are approximately related by a twofold rotation axis (2, 8). A central feature of the structural organization of the RC is the presence of 11 hydrophobic [alpha]-helixes, approximately 20-30 residues long, which are believed to represent the membrane-spanning portion of the RC (3, 9). Five membrane-spanning helixes are present in both the L and M subunits, while a single helix is in the H subunit. The folding of the L and M subunits is similar, consistent with significant sequence similarity between the two chains (19-25). The L and M subunits are approximately related by the same twofold rotation axis that relates the two cofactor branches. \n\nRCs are the first membrane proteins to be described at atomic resolution; consequently they provide an important model for discussing the folding of membrane proteins. The structure demonstrates that [alpha]-helical structures may be adopted by integral membrane proteins, and provides confirmation of the utility of hydropathy plots in identifying nonpolar membrane-spanning regions from sequence data. An important distinction between the folding environments of water-soluble proteins and membrane proteins is the large difference in water concentration surrounding the proteins. As a result, hydrophobic interactions (26) play very different roles in stabilizing the tertiary structures of these two classes of proteins; this has important structural consequences. There is a striking difference in surface polarity of membrane and water-soluble proteins. However, the characteristic atomic packing and surface area appear quite similar. \n\nA computational method is described for defining the position of the RC in the membrane (10). After localization of the RC structure in the membrane, surface residues in contact with the lipid bilayer were identified. As has been found for soluble globular proteins, surface residues are less well conserved in homologous membrane proteins than the buried, interior residues. Methods based on the variability of residues between homologous proteins are described (13); they are useful (a) in defining surface helical regions of membrane and water-soluble proteins and (b) in assigning the side of these helixes that are exposed to the solvent. A unifying view of protein structure suggests that water-soluble proteins may be considered as modified membrane proteins with covalently attached polar groups that solubilize the proteins in aqueous solution.", "date": "1989-07", "date_type": "published", "publication": "Annual Review of Biochemistry", "volume": "58", "publisher": "Annual Review of Biochemistry", "pagerange": "607-633", "id_number": "CaltechAUTHORS:REEarb89", "issn": "0066-4154", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:REEarb89", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1146/annurev.bi.58.070189.003135", "primary_object": { "basename": "REEarb89.pdf", "url": "https://authors.library.caltech.edu/records/g718a-x8204/files/REEarb89.pdf" }, "resource_type": "article", "pub_year": "1989", "author_list": "Rees, D. C.; Komiya, H.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4av0e-rfa38", "eprint_id": 54537, "eprint_status": "archive", "datestamp": "2023-08-19 21:38:24", "lastmod": "2023-10-20 16:55:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Willing-A-H", "name": { "family": "Willing", "given": "Andreas H." } }, { "id": "Georgiadis-M-M", "name": { "family": "Georgiadis", "given": "Millie M." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James Bryant" } } ] }, "title": "Cross-linking of Nitrogenase Components: Structure and Activity of the Covalent Complex", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1989 American Society for Biochemistry and Molecular Biology.\n\nReceived for publication, December 23, 1988.\n\nThis work was supported by Grants GM 34321 (to J.B. H.) and GM 31299 (to D. C.R.) from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked \"advertisement\", in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.\n\nPublished - 45_Willig_1989.pdf
", "abstract": "The nitrogenase complex from Azotobacter vinelandii is composed of the MoFe protein (Av1), an \u03b1_2\u03b2_2 tetramer, and the Fe protein (Av2), a \u03b3_2 dimer. During turnover of the enzyme, electrons are transferred from Av2 to Av1 in parallel with the hydrolysis of MgATP. Using the cross-linking reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, we have identified some of the properties of the complex between the two components. The cross-linking reaction was highly specific yielding a single apparent M_r = 97,000 protein. The amount of cross-linked product was essentially independent of whether MgATP or MgADP were in the reaction. Also, the amount was maximum at high ratios of Av2 to Av1. The M_r = 97,000 protein was characterized by amino acid analysis and Edman degradation and was found to be consistent with a 1:1 complex of an Av2 \u03b3 subunit and an Av1 \u03b2 subunit (the amino terminal serine subunit). The complex was no longer active in the nitrogenase reaction which supports, but does not prove, the requirement for dissociation of the complex after each electron transferred. Nitrogenase activity and cross-linking were inhibited in an identical way by NaCl, which suggests that electrostatic forces are critical to the formation of the electron transfer complex.", "date": "1989-05-25", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "264", "number": "15", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "8499-8503", "id_number": "CaltechAUTHORS:20150209-102138428", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-102138428", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 34321" }, { "agency": "NIH", "grant_number": "GM 31299" } ] }, "primary_object": { "basename": "45_Willig_1989.pdf", "url": "https://authors.library.caltech.edu/records/4av0e-rfa38/files/45_Willig_1989.pdf" }, "resource_type": "article", "pub_year": "1989", "author_list": "Willing, Andreas H.; Georgiadis, Millie M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/dnx7a-63n41", "eprint_id": 54538, "eprint_status": "archive", "datestamp": "2023-08-19 21:37:52", "lastmod": "2023-10-20 16:55:09", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Okamura-M-Y", "name": { "family": "Okamura", "given": "M. Y." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure and Function of Bacterial Photosynthetic Reaction Centers", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1989 Nature Publishing Group.\n\nWe thank L A. Steiner. E. Feher and D. Eisenberg for comments on the manuscript. The work presented from our laboratories has been supported by grants from the NSF and NIH. We thank the many students, postdoctoral fellows and collaborators who contributed to this work.", "abstract": "The primary reaction of photosynthesis is light-driven charge separation, carried out in reaction centres, which are complexes of integral membrane proteins and cofactors. The recent determination of the crystal structures of the reaction centres of two photosynthetic bacteria provides a basis for a quantitative understanding of the primary electron transfer processes of photosynthesis.", "date": "1989-05-11", "date_type": "published", "publication": "Nature", "volume": "339", "number": "6220", "publisher": "Nature Publishing Group", "pagerange": "111-116", "id_number": "CaltechAUTHORS:20150209-102259967", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-102259967", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF" }, { "agency": "NIH" } ] }, "doi": "10.1038/339111a0", "resource_type": "article", "pub_year": "1989", "author_list": "Feher, G.; Allen, J. P.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2tpqd-cps87", "eprint_id": 54543, "eprint_status": "archive", "datestamp": "2023-08-22 06:08:07", "lastmod": "2023-10-20 19:04:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } } ] }, "title": "Structure of the Reaction Center from Rhodopseudomonas sphaeroides R-26 and 2.4.1: Symmetry Relations and Sequence Comparisons between Different Species", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; membrane protein structure; x-ray diffraction", "note": "\u00a9 1988 National Academy of Sciences.\n\nContributed by G. Feher, August 22, 1988.\n\nWe thank E. Abresch for the preparation of the RCs and M. Y. Okamura, L. DeAntonio, and A. Chirino, for helpful discussions. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, GM31875) and the National Science Foundation (DMB85-18922 and a Presidential Young Investigators Award). D.C.R. is an A. P. Sloan Research Fellow.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U .S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 41_komiya_1988.pdf
", "abstract": "Photosynthetic reaction centers from purple bacteria exhibit an approximate twofold symmetry axis, which relates both the cofactors and the L and M subunits. For the reaction center from Rhodobacter sphaeroides, deviations from this twofold symmetry axis have been quantitated by superposing, by a 180 degrees rotation, the cofactors of the B branch onto the A branch and the M subunit onto the L subunit. An alignment of the sequences of the L and M subunits from four purple bacteria, one green bacterium, and the D_1 and D_2 subunits of a photosystem II-containing green alga is presented. The residues that are conserved in all six species are shown in relation to the structure of Rb. sphaeroides and their possible role in the function of the reaction center is discussed. A method is presented for characterizing the exposure of \u03b1-helices to the membrane based on the periodicity of conserved residues. This method may prove useful for modeling the three-dimensional structures of membrane proteins.", "date": "1988-12-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "85", "number": "23", "publisher": "National Academy of Sciences", "pagerange": "9012-9016", "id_number": "CaltechAUTHORS:20150209-103422026", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-103422026", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "NSF", "grant_number": "DMB85-18922" }, { "agency": "NSF Presidential Young Investigator Award" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "pmcid": "PMC282652", "primary_object": { "basename": "41_komiya_1988.pdf", "url": "https://authors.library.caltech.edu/records/2tpqd-cps87/files/41_komiya_1988.pdf" }, "resource_type": "article", "pub_year": "1988", "author_list": "Komiya, H.; Yeates, T. O.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yxhcs-w2x70", "eprint_id": 54541, "eprint_status": "archive", "datestamp": "2023-08-19 21:03:35", "lastmod": "2023-10-20 19:04:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Versatile Rigid-Body and Group Refinement in Real Space", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1988 International Union of Crystallography.\n\nReceived 20 January 1988; accepted 22 June 1988.\n\nWe wish to thank J. M. Rini and M. Lewis for helpful discussions and the referees for useful comments. This work was supported, in part, by USPHS grant GM31299. MATREF and additional useful programs for real-space rigid-body refinement are available upon request.\n\nPublished - 42_yeates_1988.pdf
", "abstract": "A procedure is described for performing least-squares rigid-body or group refinements in real space. The necessary derivatives are obtained from gradients in a difference Fourier map [Jack & Levitt (1978). Acta Cryst. A34, 931-935] allowing the use of fast Fourier transforms for rapid calculations. The computation time is nearly independent of the number of rigid groups being refined. The orientational transformation of the molecule or group is represented in a linear matrix form. The inherent non-linearity is treated outside of the refinement calculations, and trigonometric calculations are avoided. The linear approximation provides versatility in the types of constraints that may be applied during the refinement. Errors in unit-cell parameters may be detected through the strain component of the transformation matrix. The results of refinement of two protein structures are described as examples.", "date": "1988-12", "date_type": "published", "publication": "Journal of Applied Crystallography", "volume": "21", "number": "6", "publisher": "International Union of Crystallography", "pagerange": "925-928", "id_number": "CaltechAUTHORS:20150209-102456010", "issn": "0021-8898", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-102456010", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM31299" } ] }, "doi": "10.1107/S0021889888007927", "primary_object": { "basename": "42_yeates_1988.pdf", "url": "https://authors.library.caltech.edu/records/yxhcs-w2x70/files/42_yeates_1988.pdf" }, "resource_type": "article", "pub_year": "1988", "author_list": "Yeates, T. O. and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1yaxt-jgr78", "eprint_id": 54545, "eprint_status": "archive", "datestamp": "2023-08-22 06:05:11", "lastmod": "2023-10-20 19:04:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Chirino-A", "name": { "family": "Chirino", "given": "A." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } } ] }, "title": "Structure of the Reaction Center from Rhodopseudomonas sphaeroides R-26 and 2.4.1: Protein-Cofactor (Bacteriochlorophyll, Bacteriopheophytin and Carotenoid) Interactions", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; membrane protein structure; x-ray diffraction", "note": "\u00a9 1988 National Academy of Sciences.\n\nContributed by G. Feher, July 22, 1988.\n\nWe thank E. Abresch for the preparation of the RCs and M. Y. Okamura and W. Lubitz for helpful discussions. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, GM31875), the National Science Foundation (DMB85-18922), and a Presidential Young Investigators Award. D.C.R. is an A. P. Sloan research fellow.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 39_yeates_1988.pdf
", "abstract": "The three-dimensional structures of the cofactors and protein subunits of the reaction center (RC) from the carotenoidless mutant strain of Rhodobacter sphaeroides R-26 and the wild-type strain 2.4.1 have been determined by x-ray diffraction to resolutions of 2.8 \u00c5 and 3.0 \u00c5 with R values of 24% and 26%, respectively. The bacteriochlorophyll dimer (D), bacteriochlorophyll monomers (B), and bacteriopheophytin monomers (\u03c6) form two branches, A and B, that are approximately related by a twofold symmetry axis. The cofactors are located in hydrophobic environments formed by the L and M subunits. Differences in the cofactor-protein interactions between the A and B cofactors, as well as between the corresponding cofactors of Rb, sphaeroides and Rhodopseudomonas viridis [Michel, H., Epp, O. & Deisenhofer, J. (1986) EMBO J. 3, 2445-2451], are delineated. The roles of several structural features in the preferential electron transfer along the A branch are discussed. Two bound detergent molecules of beta-octyl glucoside have been located near B_A and B_B. The environment of the carotenoid, C, that is present in RCs from Rb. sphaeroides 2.4.1 consists largely of aromatic residues of the M subunit. A role of B_B in the triplet energy transfer from D to C and the reason for the preferential ease of removal of B_B from the RC is proposed.", "date": "1988-11-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "85", "number": "21", "publisher": "National Academy of Sciences", "pagerange": "7993-7997", "id_number": "CaltechAUTHORS:20150209-103553867", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-103553867", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "NSF", "grant_number": "DMB85-18922" }, { "agency": "NSF Presidential Young Investigator Award" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "pmcid": "PMC282340", "primary_object": { "basename": "39_yeates_1988.pdf", "url": "https://authors.library.caltech.edu/records/1yaxt-jgr78/files/39_yeates_1988.pdf" }, "resource_type": "article", "pub_year": "1988", "author_list": "Yeates, T. O.; Komiya, H.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/26feb-v9681", "eprint_id": 54544, "eprint_status": "archive", "datestamp": "2023-08-22 06:05:06", "lastmod": "2023-10-20 19:04:53", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of the Reaction Center from Rhodopseudomonas sphaeroides R-26: Protein-Cofactor (Quinones and Fe^(2+)) Interactions", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; membrane protein structure; x-ray diffraction", "note": "\u00a9 1988 National Academy of Sciences.\n\nContributed by G. Feher, August 5, 1988.\n\nWe thank E. Abresch for preparation of the RCs and M. Y. Okamura, W. Lubitz, and A. Chirino for helpful discussions. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, GM31875) and the National Science Foundation (DMB85-18922 and a Presidential Young Investigators Award). D.C.R. is an A. P. Sloan research fellow.\n\nThe publication costs of this article were defrayed in part by page charge\npayment. This article must therefore be hereby marked \"advertisement\"\nin accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 40_allen_1988.pdf
", "abstract": "The three-dimensional structure of the reaction center (RC) from Rhodobacter sphaeroides has been determined by x-ray diffraction to a resolution of 2.8 \u00c5 with an R value of 24%. The interactions of the protein with the primary quinone, Q_A, secondary quinone, Q_B, and the nonheme iron are described and compared to those of RCs from Rhodopseudomonas viridis. Structural differences between the Q_A and Q_B environments that contribute to the function of the quinones (the electron transfer from Q_A- to Q_B and the charge recombination of Q_A-, Q_B- with the primary donor) are delineated. The protein residues that may be involved in the protonation of Q_B are identified. A pathway for the doubly reduced Q_B to dissociate from the RC is proposed. The interactions between QB and the residues that have been changed in herbicide-resistant mutants are described. The environment of the nonheme iron is compared to the environments of metal ions in other proteins.", "date": "1988-11-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "85", "number": "22", "publisher": "National Academy of Sciences", "pagerange": "8487-8491", "id_number": "CaltechAUTHORS:20150209-103511705", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-103511705", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "NSF", "grant_number": "DMB85-18922" }, { "agency": "NSF Presidential Young Investigator Award" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "pmcid": "PMC282483", "primary_object": { "basename": "40_allen_1988.pdf", "url": "https://authors.library.caltech.edu/records/26feb-v9681/files/40_allen_1988.pdf" }, "resource_type": "article", "pub_year": "1988", "author_list": "Allen, J. P.; Feher, G.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tpes6-h6838", "eprint_id": 54547, "eprint_status": "archive", "datestamp": "2023-08-22 05:27:47", "lastmod": "2023-10-20 19:05:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } } ] }, "title": "Structure of the reaction center from Rhodobacter sphaeroides R-26: membrane-protein interactions", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; membrane protein structure; membrane energetics", "note": "\u00a9 1987 National Academy of Sciences.\n\nContributed by George Feher, June 2, 1987.\n\nWe thank David Eisenberg for helpful discussions. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, GM31875), the National Science Foundation (DMB85-18922, and a Presidential Young Investigators Award), and the Chicago Community Trust/ Searle Scholars Program. D.C.R. is an A. P. Sloan research fellow.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 35_yeates_1987.pdf
", "abstract": "The energetics of membrane-protein interactions are analyzed with the three-dimensional model of the photosynthetic reaction center (RC) from Rhodobacter sphaeroides. The position of the RC in the membrane and the thickness of the membrane were obtained by minimizing the hydrophobic energy with the energy function of Eisenberg and McLachlan. The 2-fold symmetry axis that relates the L and M subunits is, within the accuracy of 5 degrees, parallel to the normal of the membrane. The thickness of the membrane is estimated to be 40-45 \u00c5. Residues that are exposed to the membrane are relatively poorly conserved in the sequences of homologous RC proteins. The surface area of the RC is comparable to the surface areas of water-soluble proteins of similar molecular weight. The volumes of interior atoms in the RC are also similar to those of water-soluble proteins, indicating the same compact packing for both types of proteins. The electrostatic potential of the cofactors was calculated. The results show an asymmetry in the potential between the two possible pathways of electron transfer, with the A branch being preferred electrostatically.", "date": "1987-09-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "84", "number": "18", "publisher": "National Academy of Sciences", "pagerange": "6438-6442", "id_number": "CaltechAUTHORS:20150209-103902990", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-103902990", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "NSF", "grant_number": "DMB85-18922" }, { "agency": "NSF Presidential Young Investigator Award" }, { "agency": "Chicago Community Trust" }, { "agency": "Searle Scholars Program" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "pmcid": "PMC299092", "primary_object": { "basename": "35_yeates_1987.pdf", "url": "https://authors.library.caltech.edu/records/tpes6-h6838/files/35_yeates_1987.pdf" }, "resource_type": "article", "pub_year": "1987", "author_list": "Yeates, T. O.; Komiya, H.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qz7fn-55j66", "eprint_id": 54548, "eprint_status": "archive", "datestamp": "2023-08-22 05:27:52", "lastmod": "2023-10-20 19:05:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of the reaction center from Rhodobacter sphaeroides R-26: the protein subunits", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; membrane protein structure; x-ray diffraction; cytochrome c-reaction center complex", "note": "\u00a9 1987 National Academy of Sciences.\n\nContributed by G. Feher. May 18. 1987.\n\nWe thank E. Abresch for the preparation of the RCs. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, GM31299, and GM07185), the National Science Foundation (DMB85-18922J, a Presidential Young Investigators Award, and the Chicago Community Trust/Searle Scholars Program.\n\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 34_allen_1987.pdf
", "abstract": "The three-dimensional structure of the protein subunits of the reaction center (RC) of Rhodobacter sphaeroides has been determined by x-ray diffraction at a resolution of 2.8 \u00c5 with an R factor of 26%. The L and M subunits each contain five transmembrane helices and several helices that do not span the membrane. The L and M subunits are related to each other by a 2-fold rotational symmetry axis that is approximately the same as that determined for the cofactors. The H subunit has one transmembrane helix and a globular domain on the cytoplasmic side, which contains a helix that does not span the membrane and several \u03b2-sheets. The structural homology with RCs from other purple bacteria is discussed. A structure of the complex formed between the water soluble cytochrome c_2 and the RC from Rb. sphaeroides is proposed.", "date": "1987-09-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "84", "number": "17", "publisher": "National Academy of Sciences", "pagerange": "6162-6166", "id_number": "CaltechAUTHORS:20150209-104007322", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-104007322", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31299" }, { "agency": "NIH", "grant_number": "GM07185" }, { "agency": "NSF", "grant_number": "DMB85-18922" }, { "agency": "Chicago Community Trust" }, { "agency": "Searle Scholars Program" } ] }, "pmcid": "PMC299029", "primary_object": { "basename": "34_allen_1987.pdf", "url": "https://authors.library.caltech.edu/records/qz7fn-55j66/files/34_allen_1987.pdf" }, "resource_type": "article", "pub_year": "1987", "author_list": "Allen, J. P.; Feher, G.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1jnc2-9n228", "eprint_id": 54549, "eprint_status": "archive", "datestamp": "2023-08-22 05:24:29", "lastmod": "2023-10-20 19:05:11", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Komiya-H", "name": { "family": "Komiya", "given": "H." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Structure of the Reaction Center from Rhodopseudomonas sphaeroides R-26: The Cofactors", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; membrane protein structure; x-ray diffraction; membrane protein", "note": "\u00a9 1987 National Academy of Sciences.\n\nContributed by G. Feher, May 4, 1987.\n\nWe thank E. Abresch for the preparation of the RCs, M. Y. Okamura for helpful discussions, R. M. Sweet for assistance in the data collection at Brookhaven, and J. Deisenhofer for the FRODO dictionary. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, GM31299, and GM07185), the National Science Foundation (DMB85-18922), a Presidential Young Investigator Award, and the Chicago Community Trust/Searle Scholars Program. The crystallographic station at the Brookhaven National Laboratory was supported by the Department of Energy.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U .S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 33_allen_1987.pdf
", "abstract": "The three-dimensional structure of the cofactors of the reaction center of Rhodobacter sphaeroides R-26 has been determined by x-ray diffraction and refined at a resolution of 2.8 \u00c5 with an R value of 26%. The main features of the structure are similar to the ones determined for Rhodopseudomonas viridis [Michel, H., Epp, O. & Deisenhofer, J. (1986) EMBO J. 5, 2445-2451]. The cofactors are arranged along two branches, which are approximately related to each other by a 2-fold symmetry axis. The structure is well suited to produce light-induced charge separation across the membrane. Most of the structural features predicted from physical and biochemical measurements are confirmed by the x-ray structure.", "date": "1987-08", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "84", "number": "16", "publisher": "National Academy of Sciences", "pagerange": "5730-5734", "id_number": "CaltechAUTHORS:20150209-104057384", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-104057384", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31299" }, { "agency": "NIH", "grant_number": "GM07185" }, { "agency": "NSF", "grant_number": "DMB85-18922" }, { "agency": "Searle Scholars Program" }, { "agency": "Chicago Community Trust" }, { "agency": "Department of Energy (DOE)" } ] }, "doi": "10.1073/pnas.84.16.5730", "pmcid": "PMC298936", "primary_object": { "basename": "33_allen_1987.pdf", "url": "https://authors.library.caltech.edu/records/1jnc2-9n228/files/33_allen_1987.pdf" }, "resource_type": "article", "pub_year": "1987", "author_list": "Allen, J. P.; Feher, G.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/6rse7-d2p03", "eprint_id": 54551, "eprint_status": "archive", "datestamp": "2023-08-19 19:15:08", "lastmod": "2023-10-20 19:05:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "An Isomorphous Replacement Method for Phasing Twinned Structures", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1987 International Union of Crystallography.\n\nReceived 5 August 1985; accepted 12 May 1986.\n\nThis work was supported in part by USPHS grant GM31875 and USPHS NRS award GM07185 to TOY.\n\nPublished - 32_yeates_1987.pdf
", "abstract": "A linear least-squares formulation of the method of isomorphous replacement is presented. With data from untwinned crystals, this approach is shown to be equivalent to the phasing representation developed by Hendrickson & Lattman [Acta Cryst. (1970). B26, 136-143]. A general method for calculating the most probable phase is described and applied to the higher- dimensional problem of phase determination for twinned structures. A method for calculating the best phase with intensity data from twinned crystals is also presented. The dependences of these phasing procedures on the number of derivatives and accuracy of the data sets are evaluated in test calculations.", "date": "1987-01", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "43", "number": "1", "publisher": "International Union of Crystallography", "pagerange": "30-36", "id_number": "CaltechAUTHORS:20150209-104210949", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-104210949", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "U.S. Public Health Service", "grant_number": "GM07185" } ] }, "doi": "10.1107/S0108767387099951", "primary_object": { "basename": "32_yeates_1987.pdf", "url": "https://authors.library.caltech.edu/records/6rse7-d2p03/files/32_yeates_1987.pdf" }, "resource_type": "article", "pub_year": "1987", "author_list": "Yeates, T. O. and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rq4nt-pws29", "eprint_id": 54546, "eprint_status": "archive", "datestamp": "2023-08-19 19:07:57", "lastmod": "2023-10-20 19:05:02", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Eisenberg-D", "name": { "family": "Eisenberg", "given": "D." } }, { "id": "Wesson-M", "name": { "family": "Wesson", "given": "M." } }, { "id": "Goodsell-D", "name": { "family": "Goodsell", "given": "D." } }, { "id": "Wilcox-W", "name": { "family": "Wilcox", "given": "W." } }, { "id": "Gribskov-M", "name": { "family": "Gribskov", "given": "M." } }, { "id": "Altschuh-D", "name": { "family": "Altschuh", "given": "D." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Solvation Energy Contributions to Binding Energies", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1987 Alan R. Liss, Inc.\n\nThis work supported by NSF CHE 8509657.\n\nWe thank Drs. TC Terwilliger, A Bloomer, A Klug, ML Kopka, and RE Dickerson for use of atomic coordinates that they determined.", "abstract": "Binding affinities for the association\nof protein chains, and for the association of a drug\nto DNA, are examined with atomic salvation parameters\n(ASPs). ASPs permit an estimate of the solvation free\nenergy of binding in aqueous solution, starting from\nknown atomic coordinates. ASPs are semiempirical\ncoefficients, giving the free energy change per unit\nsurface area for the transfer of each type of chemical\ngroup from a relatively apolar environment, such as\nthe interior of a protein, to the aqueous surface.\nFor this estimate of free energy, the accessible\nsurface area of an atomic group is computed, first for\nthe free ligand and macromolecule, and then for the\ncomplex. The change in surface area is multiplied by\nthe ASP for the group and summed with terms for all\nother groups to give the standard free energy change.\nTests of the procedure are described for: (a) The\ntetramerization of melittin; (b) The formation of a\nDNA-drug complex; (c) The polymerization of tobacco\nmosaic protein subunits; and (d) The rotational isomerization of butane.", "date": "1987", "date_type": "published", "publisher": "Liss", "place_of_pub": "New York, NY", "pagerange": "203-213", "id_number": "CaltechAUTHORS:20150209-103752426", "isbn": "9780845126684", "book_title": "Protein structure, folding, and design 2", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-103752426", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CHE 8509657" } ] }, "contributors": { "items": [ { "id": "Oxender-D-L", "name": { "family": "Oxender", "given": "Dale L." } } ] }, "resource_type": "book_section", "pub_year": "1987", "author_list": "Eisenberg, D.; Wesson, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ezren-7p315", "eprint_id": 54552, "eprint_status": "archive", "datestamp": "2023-08-19 18:59:25", "lastmod": "2023-10-20 19:05:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Knossow-M", "name": { "family": "Knossow", "given": "M." } }, { "id": "Lewis-M", "name": { "family": "Lewis", "given": "M." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D." }, "orcid": "0000-0003-4073-1185" }, { "id": "Wilson-I-A", "name": { "family": "Wilson", "given": "I. A." } }, { "id": "Skehel-J-J", "name": { "family": "Skehel", "given": "J. J." } }, { "id": "Wiley-D-C", "name": { "family": "Wiley", "given": "D. C." } } ] }, "title": "The refinement of the haemagglutinin membrane glycoprotein of influenza virus", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1986 International Union of Crystallography.\n\nReceived 17 January 1986; accepted 30 June 1986.\n\nMK acknowledges support from the MRT (IPB/78), the CNRS (ATP France-USA 3/84), the Centre de Calcul Vectoriel pour le Recherche for Cray 1/S time, and the use of the LURE graphics facility. DCW acknowledges support from NIH grant\nNo. AI 13654.\n\nPublished - 31_knossow_1986.pdf
", "abstract": "The crystal structure of the haemagglutinin glycoprotein, a trimer from the membrane of influenza virus, has been refined at 3.0 \u00c5 resolution to an R\nfactor of 20.4%. The first 23 cycles were carried out on coordinates of an averaged monomer determined from a non-crystallographically threefold-symmetry-averaged electron density map. The contribution of structure factors to the least-squares equations were determined from non-crystallographically averaged gradient difference and curvature Fourier maps. The refinement was restrained using the Hendrickson & Konnert algorithm. These initial cycles were followed by 25 cycles of refinement with trigonometric evaluation of the derivatives on the complete trimer (208 422 daltons) on a Cray 1/S. Forty-eight water molecules and portions of five N-linked oligosaccharides were identified.", "date": "1986-12", "date_type": "published", "publication": "Acta crystallographica. Section B, Structural science", "volume": "42", "number": "6", "publisher": "International Union of Crystallography", "pagerange": "627-632", "id_number": "CaltechAUTHORS:20150209-104311982", "issn": "0108-7681", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150209-104311982", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AI 13654" }, { "agency": "MRT", "grant_number": "IPB/78" }, { "agency": "Centre National de la Recherche Scientifique (CNRS)" } ] }, "doi": "10.1107/S0108768186097628", "primary_object": { "basename": "31_knossow_1986.pdf", "url": "https://authors.library.caltech.edu/records/ezren-7p315/files/31_knossow_1986.pdf" }, "resource_type": "article", "pub_year": "1986", "author_list": "Knossow, M.; Lewis, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gxvnm-3t002", "eprint_id": 54636, "eprint_status": "archive", "datestamp": "2023-08-22 05:02:16", "lastmod": "2023-10-20 19:11:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Allen-J-P", "name": { "family": "Allen", "given": "J. P." } }, { "id": "Feher-G", "name": { "family": "Feher", "given": "G." } }, { "id": "Yeates-T-O", "name": { "family": "Yeates", "given": "T. O." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Deisenhofer-J", "name": { "family": "Deisenhofer", "given": "J." } }, { "id": "Michel-H", "name": { "family": "Michel", "given": "H." } }, { "id": "Huber-R", "name": { "family": "Huber", "given": "R." } } ] }, "title": "Structural Homology of Reaction Centers from Rhodopseudomonas sphaeroides and Rhodopseudomonas viridis as Determined by X-ray Diffraction", "ispublished": "pub", "full_text_status": "public", "keywords": "bacterial photosynthesis; Patterson search method; membrane protein structure; structure of bacterial reaction centers", "note": "\u00a9 1986 National Academy of Sciences.\n\nContributed by G. Feher, July 24, 1986.\n\nWe thank E. Abresch for the preparation of the RCs and H. Komiya for assistance with the data analysis. This work was supported by grants from the National Institutes of Health (AM36053, GM13191, and GM31875) and the Chicago Community Trust/Searle Scholars Program.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 30_allen_1986.pdf
", "abstract": "Crystals of the reaction center (RC) from Rhodopseudomonas sphaeroides with the space group P2_12_12_1, have been studied by x-ray diffraction. The Patterson search (molecular replacement) technique was used to analyze the data, with the structure of the reaction center from Rhodopseudomonas viridis as a model system. A preliminary electron density map of the reaction center from R. sphaeroides has been obtained. Comparison of the structure of the RC from R. sphaeroides with that from R. viridis showed the following conserved features: five membrane-spanning helices in each of the L and M subunits, a single membrane-spanning helix in the H subunit, a 2-fold symmetry axis, and similar positions and orientations of the cofactors. Unlike the RCs from R. viridis, both quinones are retained in the RCs from R. sphaeroides. The secondary quinone is located near the position related by the 2-fold symmetry axis to the primary quinone.", "date": "1986-11-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "83", "number": "22", "publisher": "National Academy of Sciences", "pagerange": "8589-8593", "id_number": "CaltechAUTHORS:20150210-094402318", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-094402318", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "AM36053" }, { "agency": "NIH", "grant_number": "GM13191" }, { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "Chicago Community Trust" }, { "agency": "Searle Scholars Program" } ] }, "pmcid": "PMC386976", "primary_object": { "basename": "30_allen_1986.pdf", "url": "https://authors.library.caltech.edu/records/gxvnm-3t002/files/30_allen_1986.pdf" }, "resource_type": "article", "pub_year": "1986", "author_list": "Allen, J. P.; Feher, G.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gq6xn-w6q24", "eprint_id": 54637, "eprint_status": "archive", "datestamp": "2023-08-19 18:39:42", "lastmod": "2023-10-20 19:11:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chakrabarti-P", "name": { "family": "Chakrabarti", "given": "P." } }, { "id": "Bernard-M", "name": { "family": "Bernard", "given": "M." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Peptide Bond Distortion and the Curvature of \u03b1-helices", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1986 John Wiley & Sons, Inc.\n\nReceived August 13, 1985; Accepted January 6, 1986.\n\nThis work was supported in part by NIH grant GM31875 and an NSF Presidential Young Investigators Award.", "abstract": "Solvent accessible peptide bonds in proteins exhibit a 1\u20133\u00b0 compression of the OCN bond angle and a corresponding expansion of the NCCa bond angle, relative to buried peptide bonds. These changes are consistent with an increase in hydrogen bonding to the carbonyl oxygen accompanying solvent exposure (J. D. Dunitz and F. K. Winkler, (1975) Acta Cryst.B31, 251\u2013263). For amphiphilic structures such as \u03b1-helices, systematic differences in peptide-bond geometry between solvent-exposed and buried residues will generate significant curvature. A decrease of 4\u00b0 in the OCN bond angle between hydrophilic and hydrophobic sides of an amphiphilic helix will lead to smooth bending, with a radius of curvature of about 70 \u00c5. This curvature is in the range observed for \u03b1-helices in proteins. Helix curvature is estimated to have only a small effect on the magnitude and direction of the helical dipole moment.", "date": "1986-06", "date_type": "published", "publication": "Biopolymers", "volume": "25", "number": "6", "publisher": "Wiley", "pagerange": "1087-1093", "id_number": "CaltechAUTHORS:20150210-094502630", "issn": "0006-3525", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-094502630", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "NSF Presidential Young Investigators Award" } ] }, "doi": "10.1002/bip.360250609", "resource_type": "article", "pub_year": "1986", "author_list": "Chakrabarti, P.; Bernard, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wcvpz-77147", "eprint_id": 54426, "eprint_status": "archive", "datestamp": "2023-08-19 18:09:09", "lastmod": "2023-10-20 16:26:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lewis-M", "name": { "family": "Lewis", "given": "Mitchell" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Fractal Surfaces of Proteins", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1985 American Association for the Advancement of Science.\n\nReceived 17 May 1985; accepted 23 September 1985.\n\nSupported in part by NIH grant GM31875, Chicago Community Trust/Searle Scholars Program, and an NSF young investigators award (D.C.R.).", "abstract": "Fractal surfaces can be used to characterize the roughness or irregularity of protein surfaces. The degree of irregularity of a surface may be described by the fractal dimension D. For protein surfaces defined with probes in the range of 1.0 to 3.5 angstroms in radius, D is approximately 2.4 or intermediate between the value for a completely smooth surface (D = 2) and that for a completely space-filling surface (D = 3). Individual regions of proteins show considerable variation in D. These variations may be related to structural features such as active sites and subunit interfaces, suggesting that surface texture may be a factor influencing molecular interactions.", "date": "1985-12-06", "date_type": "published", "publication": "Science", "volume": "230", "number": "4730", "publisher": "American Association for the Advancement of Science", "pagerange": "1163-1165", "id_number": "CaltechAUTHORS:20150205-115614621", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-115614621", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "Chicago Community Trust" }, { "agency": "Searle Scholars Program" }, { "agency": "NSF" } ] }, "doi": "10.1126/science.4071040", "resource_type": "article", "pub_year": "1985", "author_list": "Lewis, Mitchell and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fv0rx-ek879", "eprint_id": 54638, "eprint_status": "archive", "datestamp": "2023-08-22 04:23:14", "lastmod": "2023-10-20 19:11:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Electrostatic Influence on the Energetics of Electron Transfer Reactions", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme mechanisms; metalloproteins; protein electrostatics; perfect enzymes", "note": "\u00a9 1985 National Academy of Sciences.\n\nCommunicated by Paul D. Boyer, December 26, 1984.\n\nDiscussions with J.B. Howard, T. Yeates, and the University of California at Los Angeles Structural Molecular Biology group are gratefully appreciated. This work was supported by National Institutes of Health Grant GM 31875, the Dreyfus Foundation, and the Chicago Community Trust/Searle Scholars Program.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 26_rees_1985.pdf
", "abstract": "Electron transfer chains in biological systems must operate efficiently to satisfy metabolic energetic requirements. The component proteins in these chains are expected to exhibit characteristic structural features that facilitate electron transfer to the appropriate donor and acceptor proteins. A survey of soluble one-electron carrier proteins indicates a significant tendency for lower potential proteins to be more negatively charged than higher potential proteins. Consideration of the electrostatic consequences of this pattern of charge asymmetry suggests that the reduction potential difference between the two proteins will be minimized in the precursor complex associated with electron transfer. An equivalent statement is that the change in free energy accompanying electron transfer in the complex will approach zero. This behavior is consistent with theoretical arguments advanced by Albery and Knowles [Albery, W. J. & Knowles, J. R. (1976) Biochemistry 15, 5631-5640], which suggest that for the most efficient enzymes, the free energy difference between enzyme-bound species should approach zero. A more general derivation of this prediction is provided. The observed charge asymmetry in electron transfer proteins provides a structural mechanism for satisfying this requirement, thus accelerating the overall rate of electron transfer.", "date": "1985-05-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "82", "number": "10", "publisher": "National Academy of Sciences", "pagerange": "3082-3085", "id_number": "CaltechAUTHORS:20150210-094548615", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-094548615", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 31875" }, { "agency": "Camille and Henry Dreyfus Foundation" }, { "agency": "Chicago Community Trust" }, { "agency": "Searle Scholars Program" } ] }, "doi": "10.1073/pnas.82.10.3082", "pmcid": "PMC397718", "primary_object": { "basename": "26_rees_1985.pdf", "url": "https://authors.library.caltech.edu/records/fv0rx-ek879/files/26_rees_1985.pdf" }, "resource_type": "article", "pub_year": "1985", "author_list": "Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fat6f-62w86", "eprint_id": 54639, "eprint_status": "archive", "datestamp": "2023-08-19 17:44:36", "lastmod": "2023-10-20 19:11:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dickerson-J-L", "name": { "family": "Dickerson", "given": "Joyce L." } }, { "id": "Kornuc-J-J", "name": { "family": "Kornuc", "given": "John J." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Complex Formation between Flavodoxin and Cytochrome c: Cross-linking Studies", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1985 American Society for Biochemistry and Molecular Biology.\n\nReceived for publication, March 26, 1984.\n\nWe would like to thank Nguyet Tran for her\nexcellent technical assistance, and Drs. S. G. Clarke, D.S. Eisenberg,\nand A. Fowler for helpful discussions and instrumentation.\n\nThis work was supported by National Institutes of Health Grant\nGM31875, a Dreyfus Foundation Starter Grant in Chemistry, and\nthe Chicago Community Trust/Searle Scholars Program. \n\nThe costs\nof publication of this article were defrayed in part by the payment of\npage charges. This article must therefore be hereby marked \"advertisement\"\nin accordance with 18 U.S.C. Section 1734 solely to indicate\nthis fact.\n\nPublished - 25_dickerson_1985.pdf
", "abstract": "Complex formation between Azotobacter vinelandii flavodoxin and horse cytochrome c has been demonstrated through cross-linking studies with dimethyl suberimidate, dimethyl adipimidate, 1-ethyl-3-(3-di-methylaminopropyl)carbodiimide, and dimethyl-3,3'-dithiobispropionimidate. Essentially quantitative cross-linking of cytochrome c and flavodoxin was observed at low ionic strengths with the carbodiimide cross-linking reagent. An association constant of 4 X 10^4 M^(-1) was obtained between cytochrome c and flavodoxin at 88 mM ionic strength from analysis of the cross-linking studies. This value is similar to the association constant determined kinetically during the electron transfer reaction between cytochrome c and flavodoxin (Simondsen, R.P., Weber, P.C., Salemme, F.R., and Tollin, G. (1982) Biochemistry 21, 6366-6375), and suggests that the cross-linked complex may be similar to the precursor complex identified kinetically. A structural model for the flavodoxin-cytochrome c complex proposed by these workers is shown to be compatible with the present cross-linking results.", "date": "1985-04-25", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "260", "number": "8", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "5175-5178", "id_number": "CaltechAUTHORS:20150210-094659168", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-094659168", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM31875" }, { "agency": "Camille and Henry Dreyfus Foundation" }, { "agency": "Chicago Community Trust" }, { "agency": "Searle Scholars Program" } ] }, "primary_object": { "basename": "25_dickerson_1985.pdf", "url": "https://authors.library.caltech.edu/records/fat6f-62w86/files/25_dickerson_1985.pdf" }, "resource_type": "article", "pub_year": "1985", "author_list": "Dickerson, Joyce L.; Kornuc, John J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zmsyt-jnj19", "eprint_id": 54641, "eprint_status": "archive", "datestamp": "2023-08-22 04:10:42", "lastmod": "2023-10-20 19:12:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shoham-G", "name": { "family": "Shoham", "given": "G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } } ] }, "title": "Effects of pH on the Structure and Function of Carboxypeptidase A: Crystallographic Studies", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme activity; proteases; protein crystallography; activity of enzymes in solution and crystals", "note": "\u00a9 1984 National Academy of Sciences.\n\nContributed by W. N. Lipscomb, August 27, 1984.\n\nWe are grateful to Drs. R. B. Honzatko, M. Lewis, L. C. Kuo, and W. Bennett for helpful discussion and experimental assistance. We thank the National Institutes of Health (GM 06920) for support and the National Science Foundation (PCM-77-11398) for the computational facilities.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 23_shoham_1984.pdf
", "abstract": "High-resolution crystal structures are described for carboxypeptidase A (EC 3.4.17.1) in crystals grown at pH 8.5, 9.0, and 9.5 and compared with the structure at pH 7.5. The comparison shows that in the pH range of 7.5-9.5 the enzyme structure is practically unchanged, and, most importantly, that the flexible side chain of Tyr-248 remains exclusively in the \"up\" position, away from the Zn atom, throughout the pH range. There is no evidence for binding of Tyr-248 to Zn at any of these pH values. We conclude that the interaction of Tyr-248 with Zn is not an essential part of the mechanism of carboxypeptidase A and that its occurrence is an artifact of chemical modification of Tyr-248. It is also suggested that Tyr-248 is not uniquely associated with the observed high pK of the enzymatic hydrolysis.", "date": "1984-12-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "81", "number": "24", "publisher": "National Academy of Sciences", "pagerange": "7767-7771", "id_number": "CaltechAUTHORS:20150210-094928604", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-094928604", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "NSF", "grant_number": "PCM-77-11398" } ] }, "pmcid": "PMC392233", "primary_object": { "basename": "23_shoham_1984.pdf", "url": "https://authors.library.caltech.edu/records/zmsyt-jnj19/files/23_shoham_1984.pdf" }, "resource_type": "article", "pub_year": "1984", "author_list": "Shoham, G.; Rees, D. C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wn6vq-j8804", "eprint_id": 54642, "eprint_status": "archive", "datestamp": "2023-08-19 17:05:23", "lastmod": "2023-10-20 19:12:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shoham-G", "name": { "family": "Shoham", "given": "G." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } }, { "id": "Zanotti-G", "name": { "family": "Zanotti", "given": "G." } }, { "id": "Wieland-T", "name": { "family": "Wieland", "given": "Th." } } ] }, "title": "Crystal and Molecular Structure of S-Deoxo[Ile^3]amaninamide: A Synthetic Analog of Amanita Toxins", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1984 by the American Chemical Society.\n\nReceived December 22, 1983.\n\nWe thank R. Dumas for technical help in\nformatting the manuscript, the National Institutes of Health\n(Grant GM06920) for support, and the National Science Foundation\n(Grant PCM 77-1398) for initial support of the computational\nlaboratory.", "abstract": "The crystal structure of S-deoxo[Ile^3]amaninamide, a nontoxic synthetic derivative of the Amanita phalloides mushroom\ntoxins (amatoxins), has been determined by single-crystal X-ray diffraction. The crystals are monoclinic, space group P2_1,\nwith 2 formula units per unit cell. Cell dimensions are a = 12.147 \u00c5, b = 11.250 \u00c5, c = 19.267 \u00c5, and (\u03b2 = 92.41\u00b0. The\nstructure was determined by molecular replacement methods and refined by least-squares techniques to a final R value of\n0.065 for 3894 independent observations. Six intramolecular hydrogen bonds hold the bicyclic octapeptide in a compact\nconformation, which is very similar to the conformation of the naturally occurring (and toxic) amatoxin, (\u03b2-amanitin. The\nstudy demonstrates that the 30-fold reduction in binding affinity to RNA polymerase B of the title amatoxin, and probably\nof most of the other amatoxin analogues with altered side chain 3, is not due to alteration of backbone conformation. The\nthree water molecules and two ethanol molecules, crystallized with the amatoxin, form a strong and extensive intermolecular\nhydrogen-bonding system.", "date": "1984-08", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "106", "number": "16", "publisher": "American Chemical Society", "pagerange": "4606-4615", "id_number": "CaltechAUTHORS:20150210-095029990", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095029990", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM06920" }, { "agency": "NSF", "grant_number": "PCM 77-1398" } ] }, "doi": "10.1021/ja00328a051", "resource_type": "article", "pub_year": "1984", "author_list": "Shoham, G.; Rees, D. C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z2agm-nkh87", "eprint_id": 54643, "eprint_status": "archive", "datestamp": "2023-08-19 16:30:51", "lastmod": "2023-10-20 19:12:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A General Solution for the Steady-State Kinetics of Immobilized Enzyme Systems", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1984 Society for Mathematical Biology.\n\nReceived 2-17-83; Revised 6-28-83.", "abstract": "A power series solution is presented which describes the steady-state concentration profiles for substrate and product molecules in immobilized enzyme systems. Diffusional effects and product inhibition are incorporated into this model. The kinetic consequences of diffusion limitation and product inhibition for immobilized enzymes are discussed and are compared to kinetic behavior characteristic of other types of effects, such as substrate inhibition and substrate activation.", "date": "1984", "date_type": "published", "publication": "Bulletin of Mathematical Biology", "volume": "46", "number": "2", "publisher": "Springer", "pagerange": "229-234", "id_number": "CaltechAUTHORS:20150210-095125777", "issn": "0092-8240", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095125777", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1007/BF02460071", "resource_type": "article", "pub_year": "1984", "author_list": "Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7dxr6-66d43", "eprint_id": 54640, "eprint_status": "archive", "datestamp": "2023-08-19 16:30:44", "lastmod": "2023-10-20 19:11:57", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Systematic Distortion of Peptide Bond Angeles in Beta Sheets: Evidence for cis-trans Isomerization?", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1984 American Crystallographic Association.\n\nThis work was supported in part by a Dreyfus Foundation Grant in Chemistry; the donors of the Petroleum Research Foundation, administered by the American Chemical Society; and National Institutes of Health Grant GM31875.", "abstract": "With rare exceptions, peptide\nbonds at non-praline residues in\nproteins are modeled exclusively\nin the trans conformation. Energetic\nconsiderations suggest,\nhowever, that about 1% of peptide\nbonds should be in the cis conformation.\nIn cases where cis bonds\nhave been observed in proteins,\nsurprisingly little difference is\napparent between chain traces fit\nwith either cis or trans peptide\nbonds. As a result, it is possible\nthat peptide bonds in proteins\nmay exist in both the trans and\ncis conformations. In these\ncases, the electron density at a\nparticular peptide bond would be\na weighted average of both forms.\nIf a peptide bond adopts the cis\nconformation only a few percent of\nthe time, it would be impossible\nto observe these cis bonds by direct\ninspection of electron density\nmaps. During structure refinement,\nhowever, the presence of residual\ncis density should systematically\ndistort the stereochemistry of the\ntrans peptide bonds used in the\nrefinement. In this note, the\nmagnitude of this effect is estimated\nthrough model calculations\non peptides in the beta conformation.\nThe distortions in peptide\nbond angles observed in well refined\nproteins structures are\nconsistent with these bonds adopting\nthe cis conformation several\npercent of the time.", "date": "1984", "date_type": "published", "publication": "Transactions of the American Crystallographic Association", "volume": "20", "publisher": "American Crystallographic Association", "pagerange": "145-148", "id_number": "CaltechAUTHORS:20150210-094822166", "issn": "0065-8006", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-094822166", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech" }, { "agency": "American Chemical Society Petroleum Research Fund" }, { "agency": "NIH", "grant_number": "GM31875" } ] }, "resource_type": "article", "pub_year": "1984", "author_list": "Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/x8ar8-m8777", "eprint_id": 54645, "eprint_status": "archive", "datestamp": "2023-08-22 03:42:00", "lastmod": "2023-10-20 19:12:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } } ] }, "title": "Crystallographic Studies on Apocarboxypeptidase A and the Complex with Glycyl-L-Tyrosine", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme activity; proteases; protein crystallography; metalloproteins", "note": "\u00a9 1983 National Academy of Sciences.\n\nCommunicated by Konrad Bloch, August 22, 1983.\n\nWe thank the National Institutes of Health (Grant GM 06920) and the Dreyfus Foundation (D.C.R.) for support.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. \u00a71734 solely to indicate this fact.\n\nPublished - 20_rees_1983.pdf
", "abstract": "The crystal structures of zinc-free carboxypeptidase A (apocarboxypeptidase A) and the complex of glycyl-L-tyrosine with apocarboxypeptidase A are described and compared to the corresponding structures of the zinc-containing enzyme. Only small conformational changes in the zinc ligands accompany removal of the metal. Interactions between the tyrosine residue of glycyl-L-tyrosine and apocarboxypeptidase A are similar to those observed in the complex with the holoenzyme. However, in the absence of zinc, the carbonyl oxygen of the glycyl moiety now receives a hydrogen bond from the side chain of arginine-127. Although not as yet observed, a similar shift of the carbonyl oxygen of a susceptible bond from the zinc to arginine-127 could stabilize tetrahedral intermediates generated during the hydrolysis of substrates by carboxypeptidase.", "date": "1983-12-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "80", "number": "23", "publisher": "National Academy of Sciences", "pagerange": "7151-7154", "id_number": "CaltechAUTHORS:20150210-095316855", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095316855", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "Camille and Henry Dreyfus Foundation" } ] }, "pmcid": "PMC390011", "primary_object": { "basename": "20_rees_1983.pdf", "url": "https://authors.library.caltech.edu/records/x8ar8-m8777/files/20_rees_1983.pdf" }, "resource_type": "article", "pub_year": "1983", "author_list": "Rees, D. C. and Lipscomb, W. N." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z09yb-f6d27", "eprint_id": 54646, "eprint_status": "archive", "datestamp": "2023-08-19 16:18:34", "lastmod": "2023-10-20 19:12:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Largest Likely Values for R factors Calculated After Phase Refinement by Non-crystallographic Symmetry Averaging", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1983 International Union of Crystallography.\n\nReceived 22 April 1983; accepted 18 July 1983.\n\nThis work was supported by a USPHS Biomedical Research Support Grant to UCLA, and a Dreyfus Foundation Starter Grant in Chemistry.\n\nPublished - 18_rees_1983.pdf
", "abstract": "The progress of phase refinement by non-crystallographic symmetry averaging is often described by the behavior of a crystallographic R factor expressing agreement between the observed structure factors and structure factors calculated from an averaged electron density map. An upper limit for this R factor is evaluated for the case of incorrectly positioned non-crystallographic symmetry operators. Depending on the degree of non-crystallographic symmetry, the upper limit on R varies from 0.29 to 0.3, for acentric structures. Incorrect structures with the correct non-crystallographic symmetry are anticipated to converge to even lower values of R. In all cases, R values calculated for incorrect structures will be significantly lower than the value of 0.586 characteristic of wrong structures lacking non-crystallographic symmetry [Wilson (1950). Acta Cryst. 3, 397-399].", "date": "1983-11", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "39", "number": "6", "publisher": "International Union of Crystallography", "pagerange": "916-920", "id_number": "CaltechAUTHORS:20150210-095545536", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095545536", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "U.S. Public Health Service (USPHS)" }, { "agency": "Camille and Henry Dreyfus Foundation" } ] }, "doi": "10.1107/S010876738300183X", "primary_object": { "basename": "18_rees_1983.pdf", "url": "https://authors.library.caltech.edu/records/z09yb-f6d27/files/18_rees_1983.pdf" }, "resource_type": "article", "pub_year": "1983", "author_list": "Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2k406-vxg58", "eprint_id": 54644, "eprint_status": "archive", "datestamp": "2023-08-19 16:16:57", "lastmod": "2023-10-20 19:12:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Howard-J-B", "name": { "family": "Howard", "given": "James Bryant" } } ] }, "title": "Crystallization of Azotobacter vinelandii Nitrogenase Iron Protein", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1984 American Society for Biochemistry and Molecular Biology.\n\nReceived for publication, June 7, 1983.\n\nThis work was supported by Grant 5901-0410-80106 from the Science and Education Administration of the United States Department of Agriculture. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.\n\nPartially supported by the Dreyfus Foundation and the donors of the Petroleum Research Foundation, administered by the American Chemical Society.\n\nWe would like to acknowledge the hospitality of Col. W. N. Lipscomb for providing the initial x-ray diffraction facilities.\n\nPublished - 19_rees_1984.pdf
", "abstract": "The iron protein from Azotobacter vinelandii nitrogenase has been crystallized in the reduced form. The needle-shaped crystals are in space group P2_12_12 (a = 94.6 \u00c5, b = 179.9 \u00c5, c = 74.1 \u00c5) and diffract to at least 3.5-\u00c5 resolution. Five or six Fe-protein monomers are present in the asymmetric unit.", "date": "1983-10-25", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "258", "number": "20", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "12733-12734", "id_number": "CaltechAUTHORS:20150210-095211728", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095211728", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Agriculture", "grant_number": "5901-0410-80106" }, { "agency": "Camille and Henry Dreyfus Foundation" }, { "agency": "American Chemical Society Petroleum Research Fund" } ] }, "primary_object": { "basename": "19_rees_1984.pdf", "url": "https://authors.library.caltech.edu/records/2k406-vxg58/files/19_rees_1984.pdf" }, "resource_type": "article", "pub_year": "1983", "author_list": "Rees, D. C. and Howard, James Bryant" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xpfwq-92e50", "eprint_id": 54647, "eprint_status": "archive", "datestamp": "2023-08-19 16:10:16", "lastmod": "2023-10-20 19:12:28", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lewis-M", "name": { "family": "Lewis", "given": "M." } }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } } ] }, "title": "Refined Crystal Structure of Carboxypeptidase A at 1.54\u00c5 Resolution", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1983 Academic Press Inc. (London) Ltd.\n\nReceived 19 October 1982, and in revised form 18 March 1983.\n\nThis work has been supported by National Institutes of Health grant GM 06920; National Science Foundation grant PCM-77-11398 provided initial support for the computer facility. We wish to thank R. B. Honzatko for assistance in the collection of X-ray diffraction data.", "abstract": "The crystal structure of bovine carboxypeptidase A (Cox) has been refined at 1\u202254 \u00c5 resolution using the restrained least-squares algorithm of Hendrickson & Konnert (1981). The crystallographic R factor (R = \u03a3||F_o| \u2212 |F_c||/\u03a3|F_o|) for structure factors calculated from the final model is 0\u2022190. Bond lengths and bond angles in the carboxypeptidase A model have root-mean-square deviations from ideal values of 0\u2022025 \u00c5 and 3\u20226\u00b0, respectively. Four examples of a reverse turn like structure (the \"Asx\" turn) requiring an aspartic acid or asparagine residue are observed in this structure. The Asx turn has the same number of atoms as a reverse turn, but only one peptide bond, and the hydrogen bond that closes the turn is between the Asx side-chain CO group and a main-chain NH group. The distributions of CO-N and NH-O hydrogen bond angles in the \u03b1-helices and \u03b2-sheet structures of carboxypeptidase A are centered about 156\u00b0. A total of 192 water molecules per molecule of enzyme are included in the final model. Unlike the hydrogen bonding geometry observed in the secondary structure of the enzyme, the CO-O(wat) hydrogen bond angle is distributed about 131\u00b0, indicating the role of the lone pair electrons of the carbonyl oxygen in the hydrogen bond interaction. Twenty four solvent molecules are observed buried within the protein. Several of these waters are organized into hydrogen-bonded chains containing up to five waters. The average temperature factor for atoms in carboxypeptidase A is 8 \u00c5^2, and varies from 5 \u00c5^2 in the center of the protein, to over 30 \u00c5^2 at the surface.", "date": "1983-08-05", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "168", "number": "2", "publisher": "Elsevier", "pagerange": "367-387", "id_number": "CaltechAUTHORS:20150210-095701909", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095701909", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "NSF", "grant_number": "PCM-77-11398" } ] }, "doi": "10.1016/S0022-2836(83)80024-2", "resource_type": "article", "pub_year": "1983", "author_list": "Rees, D. C.; Lewis, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4dfkf-8sp07", "eprint_id": 54648, "eprint_status": "archive", "datestamp": "2023-08-19 16:05:00", "lastmod": "2023-10-20 19:12:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lewis-M", "name": { "family": "Lewis", "given": "Mitchell" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Statistical Modification of Anomalous-Scattering Differences", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1983 International Union of Crystallography.\n\nReceived 6 January 1982; accepted 7 January 1983.\n\nWe would like to thank Professor W. N. Lipscomb for providing the data-collection facilities. ML was the recipient of an American Cancer Society Fellowship.\n\nPublished - 16_lewis_1983.pdf
", "abstract": "Statistical methodology originally introduced by French & Wilson [Acta Cryst. (1978). A34, 517-525] for the treatment of negative-intensity observations is shown to be useful for the estimation of anomalous-scattering differences. The general principles of this method are described, along with applications to data from a lead derivative of the enzyme carboxypeptidase A.", "date": "1983-07", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "39", "number": "4", "publisher": "International Union of Crystallography", "pagerange": "512-515", "id_number": "CaltechAUTHORS:20150210-095749802", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095749802", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "American Cancer Society" } ] }, "doi": "10.1107/S0108767383000999", "primary_object": { "basename": "16_lewis_1983.pdf", "url": "https://authors.library.caltech.edu/records/4dfkf-8sp07/files/16_lewis_1983.pdf" }, "resource_type": "article", "pub_year": "1983", "author_list": "Lewis, Mitchell and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1sqvt-bz259", "eprint_id": 54649, "eprint_status": "archive", "datestamp": "2023-08-19 15:54:38", "lastmod": "2023-10-20 19:12:34", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas" }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Biopower", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1983 American Chemical Society.", "abstract": "The remarkable capacity of the mitochondrial electron transfer chain for generating metabolic power is compared to an electrical circuit.", "date": "1983-04", "date_type": "published", "publication": "Journal of Chemical Education", "volume": "60", "number": "4", "publisher": "American Chemical Society, Division of Chemical Education", "pagerange": "289", "id_number": "CaltechAUTHORS:20150210-095842309", "issn": "0021-9584", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095842309", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1021/ed060p289", "resource_type": "article", "pub_year": "1983", "author_list": "Rees, Douglas" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tp0ae-m5r24", "eprint_id": 54650, "eprint_status": "archive", "datestamp": "2023-08-19 15:41:16", "lastmod": "2023-10-20 19:12:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lewis-M", "name": { "family": "Lewis", "given": "Mitchell" } } ] }, "title": "Incorporation of Experimental Phases in a Restrained Least-Squares Refinement", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1983 International Union of Crystallography.\n\nReceived 7 January 1982; accepted 4 August 1982.\n\nWe would like to acknowledge the interest of Professor W. N. Lipscomb throughout this project and Professor Sir David Phillips for useful discussions. This research was supported by National Institutes of Health Grant GM 06920; National Science Foundation Grant PCM-77-11398 supported the computational\nfacilities. One of us (ML) is the recipient of an American Cancer Society postdoctoral fellowship.\n\nPublished - 14_rees_1983.pdf
", "abstract": "The least-squares refinement of macromolecular structures is characterized by a low ratio of observed data to refined parameters. Efforts have been made to compensate for this problem by incorporating subsidiary restraints into the observational equations. In this paper, a method is proposed and examples given for the introduction of additional observations into a least- squares refinement in the form of experimental phase information.", "date": "1983-01", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "39", "number": "1", "publisher": "International Union of Crystallography", "pagerange": "94-97", "id_number": "CaltechAUTHORS:20150210-095920426", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-095920426", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "NSF", "grant_number": "PCM-77-11398" }, { "agency": "American Cancer Society" } ] }, "doi": "10.1107/S0108767383000173", "primary_object": { "basename": "14_rees_1983.pdf", "url": "https://authors.library.caltech.edu/records/tp0ae-m5r24/files/14_rees_1983.pdf" }, "resource_type": "article", "pub_year": "1983", "author_list": "Rees, D. C. and Lewis, Mitchell" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/718d5-xrm42", "eprint_id": 54651, "eprint_status": "archive", "datestamp": "2023-08-19 15:19:38", "lastmod": "2023-10-20 19:12:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } } ] }, "title": "Refined Crystal Structure of the Potato Inhibitor Complex of Carboxypeptidase A at 2.5 \u00c5 Resolution", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1982 Academic Press Inc. (London) Ltd.\n\nReceived 6 October 1981, and in revised form. 13 May 1982.\n\nWe acknowledge the contribution of Dr. M. Lewis to the refinement work, and Drs. J.E. Ladner, R.C. Ladner and G. Shoham for the graphics programs. This work has been supported by National Institutes of Health grant GM-06920; National Science Foundation grant PCM-77-11398 supported the computational facilities.", "abstract": "The exopeptidase carboxypeptidase A forms a tight complex with a 39 residue inhibitor protein from potatoes. We have determined the crystal structure of this complex, and refined the atomic model to a crystallographic R-factor of 0.196 at 2.5 \u00c5 resolution. The structure of the inhibitor protein is organized around a core of disulfide bridges. No \u03b1-helices or \u03b2-sheets are present in this protein, although there is one turn of 3_(10) helix. The four carboxy-terminal residues of the inhibitor protein bind in the active site groove of carboxypeptidase A, defining binding subsites S\u2032_1, S_1, S_2 and S_3 on the enzyme. The carboxy-terminal glycine of the inhibitor is cleaved from the remainder of the inhibitor in the complex, and remains trapped in the back of the active site pocket. Interactions between the inhibitor and residues Tyr248 and Arg71 of carboxypeptidase A resemble possible features of binding stages for substrates both prior and subsequent to peptide bond hydrolysis. Not all of these interactions would be available to different types of ester substrates, however, which may be in part responsible for the observed kinetic differences in hydrolysis between peptides and various classes of esters. With the exception of residues involved in the binding of the inhibitor protein (such as Tyr248), the structure of carboxypeptidase A as determined in the inhibitor complex is quite similar to the structure of the unliganded enzyme (Lipscomb et al., 1968), which was solved from an unrelated crystal form.", "date": "1982-09-25", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "160", "number": "3", "publisher": "Elsevier", "pagerange": "475-498", "id_number": "CaltechAUTHORS:20150210-100044543", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100044543", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-06920" }, { "agency": "NSF", "grant_number": "PCM-77-11398" } ] }, "doi": "10.1016/0022-2836(82)90309-6", "resource_type": "article", "pub_year": "1982", "author_list": "Rees, D. C. and Lipscomb, W. N." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/d6r2c-78d09", "eprint_id": 54652, "eprint_status": "archive", "datestamp": "2023-08-19 14:57:12", "lastmod": "2023-10-20 19:12:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "A General Theory of X-ray Intensity Statistics for Twins by Merohedry", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1982 International Union of Crystallography.\n\nReceived 24 March 1980; accepted 17 September 1981.\n\nPublished - 12_rees_1982.pdf
", "abstract": "A general theory of X-ray intensity statistics for twins by merohedry is developed based on mathematical analogy of this problem to a one-dimensional random walk. Probability distribution functions are derived (a) for intensities from a single twinned specimen, and (b) for the differences in intensities from two separate twinned specimens. Theoretical values of a discrepancy index between observed intensities from a twin, and calculated intensities from both correct and incorrect structural models are evaluated. A new method for determining volume fractions of crystals in a twin is also proposed, based on the distribution of differences in intensities between twin-related reflections. These results have implications for the treatment of isomorphous replacement data collected from twins by hemihedry.", "date": "1982-03", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "38", "number": "2", "publisher": "International Union of Crystallography", "pagerange": "201-207", "id_number": "CaltechAUTHORS:20150210-100141163", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100141163", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1107/S056773948200045X", "primary_object": { "basename": "12_rees_1982.pdf", "url": "https://authors.library.caltech.edu/records/d6r2c-78d09/files/12_rees_1982.pdf" }, "resource_type": "article", "pub_year": "1982", "author_list": "Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xzszg-a8h77", "eprint_id": 54653, "eprint_status": "archive", "datestamp": "2023-08-22 02:46:41", "lastmod": "2023-10-20 19:12:53", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } } ] }, "title": "Binding of Ligands to the Active Site of Carboxypeptidase A", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme activity; proteases; protein crystallography; solid-state activity of enzymes; enzyme inhibition kinetics", "note": "\u00a9 1981 National Academy of Sciences.\n\nContributed by William N. Lipscomb, June 1, 1981.\n\nThis work has been supported by the National Institutes of Health Grant GM 06920; National Science Foundation Grant PCM-77-11398 supported the computational facilities.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U. S. C. \u00a7 1734 solely to indicate this fact.\n\nPublished - 11_rees_1981.pdf
", "abstract": "We compare the detailed binding modes of the 39-amino acid inhibitor from potatoes, glycyl-L-tyrosine, the ester analogue CH_3OC_6H_4(CO)CH_2CH(CO_2(-))C_6H_5, and indole acetate to the exopeptidase carboxypeptidase A (EC 3.4.17.1). In the potato inhibitor, cleavage of the COOH-terminal glycine-39 leaves a new carboxylate anion of valine-38 having one oxygen on zinc and the other as a receptor of a hydrogen bond from tyrosine-248 of carboxypeptidase. Tyrosine-248 also receives a hydrogen bond from the amide proton of the originally penultimate peptide bond between tyrosine-37 and valine-38. This hydrogen bond suggests product stabilization which is available to peptides and depsipeptides but not to esters lacking an equivalent peptide bond (nonspecific esters). Also, this structure may represent the intermediate binding step for the uncleaved substrate as it moves along the binding subsites. In particular, this may be the binding mode for the substrate after association of the COOH-terminal region of the substrate with the residues at binding subsite S_2 (tyrosine-198, phenylalanine-279, and arginine-71) and preceding entry into the catalytic site S_1'. These stabilized complexes allow some understanding of the effect of indole acetate, shown here to bind in the pocket at S_1', as a competitive inhibitor for esters (for which entry into S_1' precedes the rate-determining catalytic step for hydrolysis) and as a noncompetitive inhibitor for peptides (for which entry into S_1' is rate limiting). These results, including the binding mode of the ester analogue, are consistent with the original proposal from x-ray studies that both esters and peptides are cleaved with the carboxy terminus at S_1', although not necessarily by the same chemical steps.", "date": "1981-09", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "78", "number": "9", "publisher": "National Academy of Sciences", "pagerange": "5455-5459", "id_number": "CaltechAUTHORS:20150210-100229261", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100229261", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "NSF", "grant_number": "PCM-77-11398" } ] }, "doi": "10.1073/pnas.78.9.5455", "primary_object": { "basename": "11_rees_1981.pdf", "url": "https://authors.library.caltech.edu/records/xzszg-a8h77/files/11_rees_1981.pdf" }, "resource_type": "article", "pub_year": "1981", "author_list": "Rees, D. C. and Lipscomb, W. N." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wg21b-3t924", "eprint_id": 54654, "eprint_status": "archive", "datestamp": "2023-08-22 02:42:29", "lastmod": "2023-10-20 19:12:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lewis-M", "name": { "family": "Lewis", "given": "M." } }, { "id": "Honzatko-R-B", "name": { "family": "Honzatko", "given": "R. B." } }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "W. N." } }, { "id": "Hardman-K-D", "name": { "family": "Hardman", "given": "K. D." } } ] }, "title": "Zinc Environment and cis Peptide Bonds in Carboxypeptidase A at 1.75\u00c5 Resolution", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme catalysis; proteases; protein crystallography", "note": "\u00a9 1981 National Academy of Sciences.\n\nContributed by William N. Lipscomb, February 27, 1981.\n\nWe thank R. C. Ladner for his assistance with the graphics programs, the National Institutes of Health (GM 06920) for support of this research, the National Science Foundation (PCM 77-11398) for support of the computational facilities, and the American Cancer Society for a Postdoctoral Fellowship (N.I.L.).\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U. S. C. \u00a71734 solely to indicate this fact.\n\nPublished - 10_rees_1981.pdf
", "abstract": "The structure of the metalloenzyme carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) has been refined at 1.75 \u00c5 by a restrained least-squares procedure to a conventional crystallographic R factor of 0.162. Significant results of the refined structure relative to the catalytic mechanism are described. In the native enzyme, the zinc coordination number is five (two imidazole N delta 1 nitrogens, the two carboxylate oxygens of glutamate-72, and a water molecule). In the complex (at 2.0-\u00c5 resolution) of carboxypeptidase A with the dipeptide glycyl-L-tyrosine, however, the water ligand is replaced by both the carbonyl oxygen and the amino nitrogen of the dipeptide. The amino nitrogen also statistically occupies a second position near glutamate-270. Consequently, the coordination number of zinc may vary from five to six in carboxypeptidase A-substrate complexes. Implications of these results for the catalytic mechanism of carboxypeptidase A are discussed. In addition, three cis peptide bonds, none of which involves proline as the amino nitrogen donor, have been located fairly near the active site.", "date": "1981-06", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "78", "number": "6", "publisher": "National Academy of Sciences", "pagerange": "3408-3412", "id_number": "CaltechAUTHORS:20150210-100313332", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100313332", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "NSF", "grant_number": "PCM 77-11398" }, { "agency": "American Cancer Society" } ] }, "pmcid": "PMC319577", "primary_object": { "basename": "10_rees_1981.pdf", "url": "https://authors.library.caltech.edu/records/wg21b-3t924/files/10_rees_1981.pdf" }, "resource_type": "article", "pub_year": "1981", "author_list": "Rees, D. C.; Lewis, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tnwv9-3nn69", "eprint_id": 54656, "eprint_status": "archive", "datestamp": "2023-08-19 13:25:55", "lastmod": "2023-10-20 19:13:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Experimental Evaluation of the Effective Dielectric Constant of Proteins", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1979 Academic Press Inc. (London) Ltd.\n\nReceived 25 March 1980.\n\nWe thank W. N. Lipscomb for advice and encouragement. This work was supported by\nNational Institutes of Health grant GM06920.", "abstract": "Chemical modifications that alter the net charge of residues in reduction-oxidation proteins influence the redox potential of the protein by changing the electrostatic potential at the redox center. If the locations of the modified charges are known, the shift in redox potential may be used to determine the effective dielectric constant for the interactions between the redox center and modified residues. From the shift in redox potential upon charge neutralization of specific lysines in the hemoprotein cytochrome c, an effective dielectric constant of approximately 50 is calculated for the electrostatic interaction between the modified lysines and heme iron in the native protein.", "date": "1980-08-15", "date_type": "published", "publication": "Journal of Molecular Biology", "volume": "141", "number": "3", "publisher": "Elsevier", "pagerange": "323-326", "id_number": "CaltechAUTHORS:20150210-100445875", "issn": "0022-2836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100445875", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM06920" } ] }, "doi": "10.1016/0022-2836(80)90184-9", "resource_type": "article", "pub_year": "1980", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5pjpc-waa97", "eprint_id": 54655, "eprint_status": "archive", "datestamp": "2023-08-22 02:25:01", "lastmod": "2023-10-20 19:12:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "William N." } } ] }, "title": "Structure of the Potato Inhibitor Complex of Carboxypeptidase A at 2.5\u00c5 Resolution", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme complex; protease inhibitor; protein crystallography", "note": "\u00a9 1980 National Academy of Sciences.\n\nContributed by William N. Lipscomb, May 16, 1980.\n\nWe thank the National Institutes of Health (Grant GM 06920) for support of this research. W.N.L. also thanks the Alexander von Humboldt Foundation for an award that aided this research.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S. C. \u00a71734 solely to indicate this fact.\n\nPublished - 9_rees_1980.pdf
", "abstract": "The structure of the complex between the proteolytic enzyme carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and the 39-amino-acid carboxypeptidase A inhibitor from potatoes has been determined at 2.5-\u00c5 resolution. A combination of multiple isomorphous replacement, molecular replacement, and noncrystallographic symmetry averaging techniques was used to solve the structure. The chain trace of the inhibitor and details of the binding interactions in the complex are described. A surprising aspect of the complex is that the carboxy-terminal peptide bond of the inhibitor has been hydrolyzed, and the carboxy-terminal glycine is trapped in the binding pocket of carboxypeptidase A. Consequently, the complex resembles a stage in the catalytic mechanism after hydrolysis of the peptide bond. The ring of tyrosine-248, which is known to undergo large conformational changes upon substrate binding, is in the \"down\" position and interacts with the inhibitor in the complex.", "date": "1980-08", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "77", "number": "8", "publisher": "National Academy of Sciences", "pagerange": "4633-4637", "id_number": "CaltechAUTHORS:20150210-100406855", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100406855", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "Alexander von Humboldt Foundation" } ] }, "pmcid": "PMC349899", "primary_object": { "basename": "9_rees_1980.pdf", "url": "https://authors.library.caltech.edu/records/5pjpc-waa97/files/9_rees_1980.pdf" }, "resource_type": "article", "pub_year": "1980", "author_list": "Rees, Douglas C. and Lipscomb, William N." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/036bz-rne23", "eprint_id": 54658, "eprint_status": "archive", "datestamp": "2023-08-19 13:20:56", "lastmod": "2023-10-20 19:13:11", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "The Influence of Twinning by Merohedry on Intensity Statistics", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1980 International Union of Crystallography.\n\nReceived 7 August 1979; accepted 7 January 1980.\n\nWe would like to acknowledge the advice of R. Lesar on numerical integration techniques, the helpful comments of a referee, and the encouragement of W. N. Lipscomb. This research was supported by National Institutes of Health Grant 06920.\n\nPublished - 6_rees_1980.pdf
", "abstract": "A simple test based on intensity statistics is presented for the detection of twinning by merohedry. Using relationships derived in the text, the twinning fraction of a crystal may be estimated from the intensity probability distribution. Unlike most methods for the detection of twinning, application of this test does not require knowledge of the twinning operation. Two possible mechanisms for increasing the apparent diffraction symmetry of a crystal, twinning by merohedry and crystal disorder, may be distinguished in certain cases by these procedures.", "date": "1980-07", "date_type": "published", "publication": "Acta Crystallographica. Section A, Foundations of Crystallography", "volume": "36", "number": "4", "publisher": "International Union of Crystallography", "pagerange": "578-581", "id_number": "CaltechAUTHORS:20150210-100628171", "issn": "0108-7673", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100628171", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "06920" } ] }, "doi": "10.1107/S0567739480001234", "primary_object": { "basename": "6_rees_1980.pdf", "url": "https://authors.library.caltech.edu/records/036bz-rne23/files/6_rees_1980.pdf" }, "resource_type": "article", "pub_year": "1980", "author_list": "Rees, Douglas C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5z5sj-nx290", "eprint_id": 54657, "eprint_status": "archive", "datestamp": "2023-08-22 02:22:06", "lastmod": "2023-10-20 19:13:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Honzatko-R-B", "name": { "family": "Honzatko", "given": "Richard B." } }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "William N." } } ] }, "title": "The Structure of an Actively Exchanging Complex between Carboxypeptidase A and a Substrate Analogue", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme catalysis; proteases; protein crystallography", "note": "\u00a9 1980 National Academy of Sciences.\n\nContributed by William N. Lipscomb, March 18, 1980.\n\nWe thank E.T. Kaiser for the sample of this ketonic substrate and the National Institutes of Health, Grant GM 06920, for support of this research. W.N.L. thanks the Alexander von Humboldt Foundation for an award which facilitated this study.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U. S. C. \u00a71734 solely to indicate this fact.\n\nPublished - 7_rees_1980.pdf
", "abstract": "An x-ray diffraction study at 2.8 \u00c5 resolution has yielded the structure of a complex between bovine carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and (-)-2-benzyl-3-p-methoxybenzoylpropionic acid. This substrate is an analogue of N-(p-methoxy)-benzoylphenylalanine, in which the amide NH is replaced by CH_2. T. Sugimoto and E T. Kaiser (1979) J. Am. Chem. Soc. 101, 39469--3951] have shown that this complex catalyzes stereospecific exchange of that proton of the CH_2 group which is in the R configuration. Our structure of this complex suports the model proposed by Sugimoto and Kaiser and is very similar to the productive peptide binding mode suggested by Lipscomb et al. [Lipscomb, W. N., Hartsuck, J. A., Reeke, G. N., Quiocho, F. A., Bethge, P. A., Ludwig, M. L., Steitz, T. A., Muirhead, H. & Coppola. J. C. (1968) Brookhaven Symp. Biol. 21, 24--90]. The proposed roles of glutamic acid 270 in the proton exchange and the interaction of zinc with the carbonyl group of the substrate are consistent with the observed structure.", "date": "1980-06", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "77", "number": "6", "publisher": "National Academy of Sciences", "pagerange": "3288-3291", "id_number": "CaltechAUTHORS:20150210-100541503", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100541503", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" }, { "agency": "Alexander von Humboldt Foundation" } ] }, "pmcid": "PMC349600", "primary_object": { "basename": "7_rees_1980.pdf", "url": "https://authors.library.caltech.edu/records/5z5sj-nx290/files/7_rees_1980.pdf" }, "resource_type": "article", "pub_year": "1980", "author_list": "Rees, Douglas C.; Honzatko, Richard B.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rx6w6-36984", "eprint_id": 54659, "eprint_status": "archive", "datestamp": "2023-08-22 02:14:56", "lastmod": "2023-10-20 19:13:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Lipscomb-W-N", "name": { "family": "Lipscomb", "given": "William N." } } ] }, "title": "Structure of Potato Inhibitor Complex of Carboxypeptidase A at 5.5\u00c5 Resolution", "ispublished": "pub", "full_text_status": "public", "keywords": "enzyme complex; protease inhibitors; protein crystallography", "note": "\u00a9 1980 National Academy of Sciences.\n\nContributed by William N. Lipscomb, October 18, 1979. \n\nWe thank H. Wyckoff for advice on data collection and the National Institutes of Health (Grant GM 06920) for support.\n\nThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S. C. \u00a71734 solely to indicate this fact.\n\nPublished - 5_rees_1980.pdf
", "abstract": "The complex of the 39-amino inhibitor (potato) of bovine carboxypeptidase A (carboxypeptidase; peptidyl-L-amino-acid hydrolase, EC 3.4.12.2) was crystallized in space group P3_2. There are two protein-inhibitor complexes in the asymmetric unit. These crystals exhibited pseudo-P32_21 symmetry due to twinning about the a_3 axis. Heavy atom difference Patterson maps and rotation functions indicated, however, that the noncrystallographic twofold axis that relates these two complexes is nearly coincident with the a_3 axis. Consequently, to a good approximation at low resolution, the space group of the complex is P3_221 and the effects of twinning may be ignored. The structure was solved by using multiple isomorphous replacement and molecular replacement techniques. At 5.5-\u00c5 resolution, the multiple isomorphous replacement map was readily interpretable in terms of the known native carboxypeptidase A structure plus extra density around the active site. The position of this extra density is consistent with the binding mode for extended substrate proposed from earlier model building studies with the native enzyme (Lipscomb, W.N., Hartsuck, J.A., Reeke, G.N., Quiocho, F.A. Bethge, P.H., Ludwig, M.L., Steitz, T.A., Muirhead, H. & Coppola, J.C. (1968) Brookhaven Symp. Biol. 21, 24-90).", "date": "1980-01", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "77", "number": "1", "publisher": "National Academy of Sciences", "pagerange": "277-280", "id_number": "CaltechAUTHORS:20150210-100728083", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100728083", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM 06920" } ] }, "doi": "10.1073/pnas.77.1.277", "pmcid": "PMC348252", "primary_object": { "basename": "5_rees_1980.pdf", "url": "https://authors.library.caltech.edu/records/rx6w6-36984/files/5_rees_1980.pdf" }, "resource_type": "article", "pub_year": "1980", "author_list": "Rees, Douglas C. and Lipscomb, William N." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gxvmf-34892", "eprint_id": 54660, "eprint_status": "archive", "datestamp": "2023-08-19 09:54:05", "lastmod": "2023-10-20 19:13:17", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chan-Shung-Kai", "name": { "family": "Chan", "given": "Shung Kai" } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Li-Su-Chen", "name": { "family": "Li", "given": "Su-Chen" } }, { "id": "Li-Yu-Teh", "name": { "family": "Li", "given": "Yu-Teh" } } ] }, "title": "Linear Structure of the Oligosaccharide Chains in \u03b1_1-Protease Inhibitor Isolated from Human Plasma", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1976 American Society for Biochemistry and Molecular Biology.\n\nReceived for publication, December 9, 1974 and in revised form, May 1, 1975.\n\nThis work was supported in part by Research Grants HL 16166\nfrom the National Institutes of Health (to S. K. C.) and National Science Foundation Grant GB 43571 (to Y.T. L.).\n\nPublished - 4_chan_1976.pdf
", "abstract": "Two glycopeptides present in equal amounts were isolated from a pronase digest of alpha1-protease inhibitor of human plasma by gel filtration on Sephadex G-50 and chromatography on DEAE-cellulose. The carbohydrate side chains in both glycopeptides are linked through asparaginyl residues. The glycopeptides were digested sequentially with specific glycosidases; and after each step, the released sugars as well as the composition of the residual peptides were determined. The linear structures of these glycopeptides deduced from these data are shown below. Based on the total carbohydrate content of the intact protein and with these structural data, it is postulated that 4 oligosaccharide units are attached to 1 molecule of the protein; 2 of these were represented as in Equation 1, the other 2 as in Equation 2.", "date": "1976-01-25", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "251", "number": "2", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "471-476", "id_number": "CaltechAUTHORS:20150210-100848506", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100848506", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "HL 16166" }, { "agency": "NSF", "grant_number": "GB 43571" } ] }, "primary_object": { "basename": "4_chan_1976.pdf", "url": "https://authors.library.caltech.edu/records/gxvmf-34892/files/4_chan_1976.pdf" }, "resource_type": "article", "pub_year": "1976", "author_list": "Chan, Shung Kai; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jhbbx-6hk13", "eprint_id": 54661, "eprint_status": "archive", "datestamp": "2023-08-19 09:25:41", "lastmod": "2023-10-20 19:13:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chan-Shung-Kai", "name": { "family": "Chan", "given": "S. K." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "D. C." }, "orcid": "0000-0003-4073-1185" } ] }, "title": "Molecular Basis for the \u03b1_1-Protease Inhibitor Deficiency", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1975 Nature Publishing Group.\n\nReceived January 27; revised April 2, 1975.\n\nThis research was supported by a grant from the National Institutes of Health. We thank Drs R. Talamo and J. Pierce for performing the electrophoresis in their laboratories and for providing serum from ZZ individuals.", "abstract": "The \u03b1_1-protease inhibitor (formerly \u03b11-antitrypsin) is in herited by a series of autosomal codominant alleles that determine its concentration and electrophoretic mobility. Serum from individuals with severe \u03b11-protease inhibitor deficiency usually contains an electrophoretically slow-moving \u03b1_1-protease inhibitor (type ZZ) in an amount 10\u201340% of that found in the normal population (type MM). This deficient state is associated with either an early-onset form of familial emphysema or familial infantile cirrhosis.", "date": "1975-05-15", "date_type": "published", "publication": "Nature", "volume": "255", "number": "5505", "publisher": "Nature Publishing Group", "pagerange": "240-241", "id_number": "CaltechAUTHORS:20150210-100937554", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-100937554", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" } ] }, "doi": "10.1038/255240a0", "resource_type": "article", "pub_year": "1975", "author_list": "Chan, S. K. and Rees, D. C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rd5kt-agd22", "eprint_id": 54662, "eprint_status": "archive", "datestamp": "2023-08-19 09:17:19", "lastmod": "2023-10-20 19:13:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Slayman-C-W", "name": { "family": "Slayman", "given": "Carolyn W." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Orchard-P-P", "name": { "family": "Orchard", "given": "Pamela P." } }, { "id": "Slayman-C-L", "name": { "family": "Slayman", "given": "Clifford L." } } ] }, "title": "Generation of Adenosine Triphosphate in Cytochrome-deficient Mutants of Neurospora", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1975 American Society for Biochemistry and Molecular Biology.\n\nReceived for publication, May 20, 1974.\n\nThis work was supported by Research Grants GM-15761 and GM-15858 and by Research Career Development Awards GM-20163 and GM-20164 from the National Institute of General Medical Sciences.\n\nThe authors are indebted to Dr. Alan Lambowitz and Dr. Dietrich Gradmann for their many helpful discussions.\n\nPublished - 2_slayman_1974.pdf
", "abstract": "The fungus Neurospora crassa is known to possess a branched respiratory system consisting of the standard cytochrome chain and a cyanide-insensitive alternate oxidase. In the present experiments, the physiological function of the alternate oxidase has been analyzed by taking advantage of a number of cytochrome-deficient mutants, particularly poky f. Respiration, cellular ATP levels, and growth have been examined under the influence of three classes of inhibitors: inhibitors of the cytochrome chain (antimycin, cyanide), an inhibitor of the laternate oxidase (salicyl hydroxamic acid), and an uncoupling agent (carbonyl cyanide m-chlorophenylhydrazone). The results indicate that the over-all efficiency of the alternate oxidase in producing ATP and supporting growth is much less than that of the cytochrome chain. Depending upon the amount of oxidative phosphorylation at Sites II and III in the cytochrome chain, which varies from strain to strain, the efficiency of the alternate oxidase relative to that of the cytochrome chain ranges from 13% in wild type Neurospora to 18 to 21% in poky f, 35% in mi-3, and 57% in cyt-2. A comparison of the short term effects of cyanide and carbonyl cyanide m-chlorophenylhydrazone on cellular ATP in poky f suggests that, during respiration through the alternate oxidase, ATP can be produced both by substrate-level phosphorylation (accompanying glycolysis and the oxidation of alpha-ketoglutarate) and by oxidative phosphorylation at Site I. When cells are grown on sucrose, as much as 22% of ATP synthesis in the presence of cyanide occurs at Site I. When cells are grown on acetate to diminish the rate of glycolysis, the contribution of Site I becomes proportionately larger. Both the growth experiments and the short term inhibitor experiments reveal that ATP levels in Neurospora are kept high be a feedback process which depresses ATP breakdown (and growth) very quckly after ATP synthesis is inhibited. Thus, poky f grows more slowly that wild type Neurospora and is inhibited still further when either the cytochrome chain or the alternate oxidase is blocked. Under all of these conditions, however, cellular ATP in poky f is maintained at a high level (about 3 mmol per kg of cell water, slightly above the values measured in the wild type strain).", "date": "1975-01-25", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "250", "number": "2", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "396-408", "id_number": "CaltechAUTHORS:20150210-101019010", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-101019010", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Institute of General Medical Sciences", "grant_number": "GM-15761" }, { "agency": "National Institute of General Medical Sciences", "grant_number": "GM-15858" }, { "agency": "National Institute of General Medical Sciences", "grant_number": "GM-20163" }, { "agency": "National Institute of General Medical Sciences", "grant_number": "GM-20164" } ] }, "primary_object": { "basename": "2_slayman_1974.pdf", "url": "https://authors.library.caltech.edu/records/rd5kt-agd22/files/2_slayman_1974.pdf" }, "resource_type": "article", "pub_year": "1975", "author_list": "Slayman, Carolyn W.; Rees, Douglas C.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1b7g8-wx444", "eprint_id": 54663, "eprint_status": "archive", "datestamp": "2023-08-19 08:57:05", "lastmod": "2023-10-20 19:13:28", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lester-R-L", "name": { "family": "Lester", "given": "Robert L." } }, { "id": "Smith-S-W", "name": { "family": "Smith", "given": "Sharron W." } }, { "id": "Wells-G-B", "name": { "family": "Wells", "given": "Gerald B." } }, { "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185" }, { "id": "Angus-W-W", "name": { "family": "Angus", "given": "Wallace W." } } ] }, "title": "The Isolation and Partial Characterization of Two Novel Sphingolipids from Neurospora crassa: Di(Inositolphosphoryl)ceramide and [(gal)_3glu]ceramide", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1974 American Society for Biochemistry and Molecular Biology.\n\nReceived for publication, September 4, 1973.\n\nThis research was supported in part by Grant NB08323 from the National Institutes of Health.\n\nPublished - 1_lester_1975.pdf
", "abstract": "Neurospora crassa strains labeled uniformly with ^(32)P_i and [^3H]inositol exhibit at least six phospholipid components containing ^3H when separated by paper chromatography. One of the major components is phosphatidylinositol. Other components, which account for 40 to 60% of the lipid-extractable ^3H in various strains, are stable to mild alkaline methanolysis and appear to be sphingolipids with equivalent amounts of inositol and phosphorus. The major phosphosphingolipid was purified by means of differential solubility and by column chromatography on porous silica beads. This substance contains equivalent amounts of hydroxysphinganine and hydroxytetracosanoic acid and 2 eq each of myoinositol, phosphorus, and sodium. Alkaline degradation yielded 2 eq of inositol monophosphate and periodate degradation gave a C-15 fragment. The elemental composition of this compound also fits the formulation, (inositol-P)_2-ceramide.\nA [^3H]inositol pulse-chase experiment carried out with an inositol-requiring mutant in exponential growth shows labeled inositol accumulating in the sphingolipid accompanied by decreased labeling in phosphatidylinositol and the acid-soluble fraction. These changes also occur when the chase is carried out during inositol starvation suggesting that degradation of phosphatidylinositol and formation of sphingolipid occurs in the absence of growth.\nA neutral glycosphingolipid was also obtained as a by-product of the phospholipid purification. This substance is provisionally formulated as the ceramide tetrahexoside: [(gal)_3glu]-N-hydroxytetracosonyl-hydroxysphinganine.", "date": "1974-06-10", "date_type": "published", "publication": "Journal of Biological Chemistry", "volume": "249", "number": "11", "publisher": "American Society for Biochemistry and Molecular Biology", "pagerange": "3388-3394", "id_number": "CaltechAUTHORS:20150210-101059981", "issn": "0021-9258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150210-101059981", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NB08323" } ] }, "primary_object": { "basename": "1_lester_1975.pdf", "url": "https://authors.library.caltech.edu/records/1b7g8-wx444/files/1_lester_1975.pdf" }, "resource_type": "article", "pub_year": "1974", "author_list": "Lester, Robert L.; Smith, Sharron W.; et el." } ]