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.
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.
|Yi, Feng; Mou, Tung-Chung; Dorsett, Katherine N et al. (2016) Structural Basis for Negative Allosteric Modulation of GluN2A-Containing NMDA Receptors. Neuron 91:1316-29|
|Kang, Hyunook; Weiss, Thomas M; Bang, Injin et al. (2016) Structure of the Intermediate Filament-Binding Region of Desmoplakin. PLoS One 11:e0147641|
|Tysoe, Christina; Williams, Leslie K; Keyzers, Robert et al. (2016) Potent Human Î±-Amylase Inhibition by the Î²-Defensin-like Protein Helianthamide. ACS Cent Sci 2:154-161|
|Baxter, Elizabeth L; Aguila, Laura; Alonso-Mori, Roberto et al. (2016) High-density grids for efficient data collection from multiple crystals. Acta Crystallogr D Struct Biol 72:2-11|
|Stoisser, Thomas; Brunsteiner, Michael; Wilson, David K et al. (2016) Conformational flexibility related to enzyme activity: evidence for a dynamic active-site gatekeeper function of Tyr(215) in Aerococcus viridans lactate oxidase. Sci Rep 6:27892|
|Kowalska, Joanna K; Hahn, Anselm W; Albers, Antonia et al. (2016) X-ray Absorption and Emission Spectroscopic Studies of [L2Fe2S2](n) Model Complexes: Implications for the Experimental Evaluation of Redox States in Iron-Sulfur Clusters. Inorg Chem 55:4485-97|
|Zhao, Haiyan; Speir, Jeffrey A; Matsui, Tsutomu et al. (2016) Structure of a Bacterial Virus DNA-Injection Protein Complex Reveals a Decameric Assembly with a Constricted Molecular Channel. PLoS One 11:e0149337|
|Warner, Thomas; Jalilehvand, Farideh (2016) Formation of Hg(II) Tetrathiolate Complexes with Cysteine at Neutral pH. Can J Chem 94:373-379|
|Kobylarz, Marek J; Grigg, Jason C; Liu, Yunan et al. (2016) Deciphering the Substrate Specificity of SbnA, the Enzyme Catalyzing the First Step in Staphyloferrin B Biosynthesis. Biochemistry 55:927-39|
|Hackos, David H; Lupardus, Patrick J; Grand, Teddy et al. (2016) Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron 89:983-99|
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