Synchrotron radiation (SR) is an extremely bright and tunable x-ray source that enables forefront research in Structural molecular biology (SMB). A """"""""Synchrotron Structural Biology Resource"""""""" is supported at the Stanford Synchrotron Radiation Lightsource (SSRL) by the NIH and DOE to develop new technologies in macromolecular crystallography, x-ray absorption spectroscopy and small angle x-ray scattering/diffraction, to train/support users, and to disseminate these capabilities to the biomedical research community. This proposal is for the continued funding, operation and future development of this Resource. New initiatives will capitalize on the increasing SR performance of SSRL's 3rd generation storage ring SPEARS. Proposed also is the development of selected SMB applications of the world's first x-ray free-electron laser (LCLS), just beginning operation at SLAC. A principal aim is to optimize experimental facilities and instrumentation, detectors, software and compute performance on the 9+ SMB dedicated beam lines at SSRL (with another two in construction) to take full advantage of the high brightness provided by SPEAR3 at 500 mA current. This will enable the Resource to advance the scientific forefront with new initiatives built upon state-of-the-art instrumentation and methodologies, innovative software and automated/high-throughput systems for: studying high resolution structures/function of large, complex blomolecules and molecular machines;imaging the spatial distribution and chemical nature of elements in non-crystalline biological materials;investigating fundamental questions in biophysics such as protein and RNA folding;and developing/improving methods for studying very fast time-resolved structural changes in chemical and biological systems with ultrafast or fast scattering and absorption techniques. These scientific advancements will be facilitated by parallel developments in software to provide expanded capabilities for instrument and detector control, remote data collection and real-time data analysis. Driving biomedical projects and collaborative research programs involving a large number of outside scientists will drive and support core technological developments, the pace of translational research will be accelerated through collaborations with NCRR CTSA Centers, and a highly active program in training and dissemination will bring them to a wide user community.

Public Health Relevance

is to a number of important biological problems including the structure of enzymes, metalloproteins, membrane-bound proteins and immunoglobulins;the active site structure of metalloproteins involved in metabolism and photosynthesis;and how these structures change in different states or evolve in time as reactions or events like protein folding or conformational changes occur. Such information is more broadly important to the health-related areas of drug design, cancer research, and virology.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-P (40))
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Swain, Amy L
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Stanford University
Schools of Arts and Sciences
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Jennings, Gareth K; Hsu, Mei-Hui; Shock, Lisa S et al. (2018) Noncovalent interactions dominate dynamic heme distortion in cytochrome P450 4B1. J Biol Chem 293:11433-11446
Jackson, David R; Shakya, Gaurav; Patel, Avinash B et al. (2018) Structural and Functional Studies of the Daunorubicin Priming Ketosynthase DpsC. ACS Chem Biol 13:141-151
Sibener, Leah V; Fernandes, Ricardo A; Kolawole, Elizabeth M et al. (2018) Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding. Cell 174:672-687.e27
Fan, Ruixi; Serrano-Plana, Joan; Oloo, Williamson N et al. (2018) Spectroscopic and DFT Characterization of a Highly Reactive Nonheme FeV-Oxo Intermediate. J Am Chem Soc 140:3916-3928
Bowden, Catherine F M; Chan, Anson C K; Li, Emily J W et al. (2018) Structure-function analyses reveal key features in Staphylococcus aureus IsdB-associated unfolding of the heme-binding pocket of human hemoglobin. J Biol Chem 293:177-190
Moon, Thomas M; D'Andréa, Éverton D; Lee, Christopher W et al. (2018) The structures of penicillin-binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into ?-lactam resistance. J Biol Chem 293:18574-18584
Bitra, Aruna; Doukov, Tzanko; Wang, Jing et al. (2018) Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling. J Biol Chem 293:1317-1329
Chiang, Linus; Wasinger, Erik C; Shimazaki, Yuichi et al. (2018) Electronic Structure and Reactivity Studies of a Nonsymmetric One-Electron Oxidized CuII Bis-phenoxide Complex. Inorganica Chim Acta 481:151-158
Moon, Thomas M; Sheehe, Jessica L; Nukareddy, Praveena et al. (2018) An N-terminally truncated form of cyclic GMP-dependent protein kinase I? (PKG I?) is monomeric and autoinhibited and provides a model for activation. J Biol Chem 293:7916-7929
Sharma, Pankaj; Maklashina, Elena; Cecchini, Gary et al. (2018) Crystal structure of an assembly intermediate of respiratory Complex II. Nat Commun 9:274

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