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 proposed for continuing support at the Stanford Synchrotron Radiation Light source. (SSRL) by the NIH NIGMS and DOE BER to develop new technologies in macromolecular crystallography, x-ray absorption/emission spectroscopy and small angle x-ray scattering/diffraction, to train/support users, and to disseminate the newly developed capabilities to the biomedical research community. This proposal is for the continued funding, operation and future development of this SMB Resource. New initiatives will capitalize on the increasing SR performance of SSRL's 3rd generation storage ring SPEAR3. Proposed also is the development of selected SMB applications of LCLS. A principal aim is to optimize experimental facilities and instrumentation, detectors, software and compute performance on the SMB Resource's 9+ beam lines at SSRL (with another two in construction) to take full advantage of the high brightness provided by SPEAR3 at 500 mA current and provide innovative new instrumentation and methodologies. This will enable the SMB 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 biomolecules and molecular machines; investigating fundamental questions in biophysics such as protein folding; and developing/improving methods for studying very fast time-resolved structural changes in chemical and biological systems with ultrafast or fast scattering and spectroscopy 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 and service programs involving a large number of outside scientists will drive and support core technological developments.

Public Health Relevance

is to a number of important biological problems including the structure of enzymes, metalloproteins, membrane-bound proteins and viruses; 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)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Smith, Ward
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Arts and Sciences
United States
Zip Code
Mei, Xianghan; Alvarez, Jonathan; Bon Ramos, Adriana et al. (2017) Crystal structure of the archaeosine synthase QueF-like-Insights into amidino transfer and tRNA recognition by the tunnel fold. Proteins 85:103-116
Remesh, Soumya G; Andreatta, Massimo; Ying, Ge et al. (2017) Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT. J Biol Chem 292:5262-5270
Porter, Nicholas J; Mahendran, Adaickapillai; Breslow, Ronald et al. (2017) Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors. Proc Natl Acad Sci U S A 114:13459-13464
Orlova, Natalia; Gerding, Matthew; Ivashkiv, Olha et al. (2017) The replication initiator of the cholera pathogen's second chromosome shows structural similarity to plasmid initiators. Nucleic Acids Res 45:3724-3737
Nold, Shiloh M; Lei, Haotian; Mou, Tung-Chung et al. (2017) Effect of a K72A Mutation on the Structure, Stability, Dynamics, and Peroxidase Activity of Human Cytochrome c. Biochemistry 56:3358-3368
Sathiyamoorthy, Karthik; Jiang, Jiansen; Möhl, Britta S et al. (2017) Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies. Proc Natl Acad Sci U S A 114:E8703-E8710
Morrison, Christine N; Spatzal, Thomas; Rees, Douglas C (2017) Correction to Reversible Protonated Resting State of the Nitrogenase Active Site. J Am Chem Soc 139:13958
Chen, Eric Sheng-Wen; Weng, Jui-Hung; Chen, Yu-Hou et al. (2017) Phospho-Priming Confers Functionally Relevant Specificities for Rad53 Kinase Autophosphorylation. Biochemistry 56:5112-5124
Khorasani-Motlagh, Mozhgan; Lacasse, Michael J; Zamble, Deborah B (2017) High-affinity metal binding by the Escherichia coli [NiFe]-hydrogenase accessory protein HypB is selectively modulated by SlyD. Metallomics 9:482-493
Collins, Bernard C; Gunn, Robin J; McKitrick, Tanya R et al. (2017) Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates. Structure 25:1667-1678.e4

Showing the most recent 10 out of 542 publications