Funding is requested to replace a 14-year-old Rigaku X-ray diffraction system, including replacing the existing Rigaku (two-port) RU-H3R rotating anode X-ray generator with a Rigaku (single-port) MicroMax-003 sealed tube X-ray generator, replacing the two R-AxisIV imaging plate detectors with one Saturn 165+ CCD detector, and replacing the two existing X-stream cryo systems with one Oxford Cobra cryo system. The two existing Osmic mirror systems and R-AxisIVs will be traded in for credit towards this new X-ray facility. The requested instrument is essential to the specific aims of the NIH-funded research of the major users of this system, which includes studying the molecular mechanisms of enzymes involved in fatty acid metabolism, proteins involved in pre-mRNA 3'-end processing and RNA polymerase II transcription initiation and termination, Ca2+ and TRPC channels, epigenetic regulation by PWWP domain proteins, proteins involved in transmembrane transport and oxidative DNA damage repair, development of new methods for determining structures of proteins by solid state NMR, mechanism of inhibition of small molecules directed against proteins with important roles in human diseases, and structural genomics on eukaryotic, especially human, proteins and their prokaryotic homologs.
X-ray crystallography provides information at the atomic level about the functions of biological macromolecules. The requested instrument will be a crucial component of research on proteins of fundamental biological importance, as well as structure-based drug discovery against human diseases (obesity, diabetes, cancer and others).
|Dieck, Chelsea L; Tzoneva, Gannie; Forouhar, Farhad et al. (2018) Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia. Cancer Cell 34:136-147.e6|
|Zhang, Yinglu; Shan, Chun-Min; Wang, Jiyong et al. (2017) Molecular basis for the role of oncogenic histone mutations in modulating H3K36 methylation. Sci Rep 7:43906|
|Choi, Philip H; Vu, Thu Minh Ngoc; Pham, Huong Thi et al. (2017) Structural and functional studies of pyruvate carboxylase regulation by cyclic di-AMP in lactic acid bacteria. Proc Natl Acad Sci U S A 114:E7226-E7235|
|Luo, Shukun; Tong, Liang (2017) Molecular mechanism for the regulation of yeast separase by securin. Nature 542:255-259|
|Welsch, Matthew E; Kaplan, Anna; Chambers, Jennifer M et al. (2017) Multivalent Small-Molecule Pan-RAS Inhibitors. Cell 168:878-889.e29|
|Maderbocus, Riyaz; Fields, Blanche L; Hamilton, Keith et al. (2017) Crystal structure of a Pseudomonas malonate decarboxylase holoenzyme hetero-tetramer. Nat Commun 8:160|
|Wu, Yixuan; Albrecht, Todd R; Baillat, David et al. (2017) Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance. Proc Natl Acad Sci U S A 114:4394-4399|
|McFarland, Adelle P; Luo, Shukun; Ahmed-Qadri, Fariha et al. (2017) Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-?B Activation and Shapes a Proinflammatory Antibacterial State. Immunity 46:433-445|
|Aik, Wei Shen; Lin, Min-Han; Tan, Dazhi et al. (2017) The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing. PLoS One 12:e0186034|
|Harriman, Geraldine; Greenwood, Jeremy; Bhat, Sathesh et al. (2016) Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci U S A 113:E1796-805|
Showing the most recent 10 out of 25 publications