Replacement of an aging X-ray diffraction system for protein crystallography

描述（申请人提供）：申请资金用于更换一个已有14年历史的理学X射线衍射系统，包括更换现有的理学（双端口）RU-H3 R旋转阳极X射线发生器，配备理学（单端口）MicroMax-003密封管X射线发生器，将两个R-AxisIV成像板探测器替换为一个Saturn 165+ CCD探测器，用一个牛津眼镜蛇低温系统取代现有的两个X流低温系统。现有的两个Osmic反射镜系统和R-AxisIV将被用于这一新的X射线设施。所要求的仪器对于该系统主要用户的NIH资助研究的特定目标至关重要，其中包括研究参与脂肪酸代谢的酶的分子机制，参与前mRNA 3 '端加工和RNA聚合酶II转录起始和终止的蛋白质，Ca 2+和TRPC通道，PWWP结构域蛋白的表观遗传调节，涉及跨膜转运和氧化DNA损伤修复的蛋白质，通过固态NMR确定蛋白质结构的新方法的开发，针对在人类疾病中具有重要作用的蛋白质的小分子抑制机制，以及真核生物，特别是人类，蛋白质及其原核同源物。 公共卫生相关性：X射线晶体学在原子水平上提供有关生物大分子功能的信息。所要求的仪器将是研究具有基本生物重要性的蛋白质以及针对人类疾病（肥胖症，糖尿病，癌症等）的基于结构的药物发现的关键组成部分。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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).