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

更换老化的蛋白质晶体学 X 射线衍射系统

• 批准号: 8247298
• 负责人: LIANG TONG
• 金额: $ 40.53万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247298
• 关键词: 14 year old; Aging; Anodes; Cobra; Crystallography; DNA Repair; Development; Epigenetic Process; Funding; Funding Applicant; Homologous Gene; Human; Image; Methods; Molecular; Organized by Structure Protein; PWWP Domain; Process; Proteins; RNA Polymerase II; Regulation; Research; Roentgen Rays; Role; Saturn; Stream; System; Transcription Initiation; Transmembrane Transport; Tube; United States National Institutes of Health; X ray diffraction analysis; X-Ray Diffraction; detector; enzyme mechanism; fatty acid metabolism; human disease; instrument; mRNA Precursor; oxidative DNA damage; seal; small molecule; solid state nuclear magnetic resonance; structural genomics; transcription termination

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).

说明(由申请人提供)：申请资金以取代已有14年历史的Rigaku X射线衍射系统，包括用Rigaku(单端口)MicroMax-003密封管X射线发生器取代现有的Rigaku(双端口)RU-H3R旋转阳极X射线发生器，用一个土星165+CCD探测器取代两个R-AxisIV成像板探测器，以及用一个牛津眼镜蛇冷冻系统取代现有的两个X流冷冻系统。现有的两个渗透镜系统和R-AxisIV将被用来换取这个新的X射线设备的信用。所要求的仪器对于NIH资助的该系统主要用户的研究的特定目标是必不可少的，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转录启动和终止的蛋白质，钙和TRPC通道，PWWP结构域蛋白质的表观遗传调节，参与跨膜运输和氧化DNA损伤修复的蛋白质，开发固体核磁共振确定蛋白质结构的新方法，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系物的结构基因组学。 与公众健康相关：X射线结晶学在原子水平上提供有关生物大分子功能的信息。所要求的仪器将是具有基本生物学意义的蛋白质研究的重要组成部分，以及针对人类疾病(肥胖症、糖尿病、癌症和其他)的基于结构的药物发现。

项目成果

Exploring the Molecular Structural Requirements of Flavonoids as Beta- Secretase-1 Inhibitors Using Molecular Modeling Studies.

利用分子模型研究探索类黄酮作为 Beta-Secretase-1 抑制剂的分子结构要求。

• DOI: 10.2174/1570163820666230329090424
• 发表时间: 2023
• 期刊: Current drug discovery technologies
• 作者: More,UttamA;Noolvi,MalleshappaN;Kumar,Devendra;Tripathi,Avanish
• 通讯作者: Tripathi,Avanish

Structure of the Arabidopsis thaliana TOP2 oligopeptidase.

拟南芥 TOP2 寡肽酶的结构。

• DOI: 10.1107/s2053230x14006128
• 发表时间: 2014
• 期刊: Acta crystallographica. Section F, Structural biology communications
• 作者: Wang,Ruiying;Rajagopalan,Krithika;Sadre-Bazzaz,Kianoush;Moreau,Magali;Klessig,DanielF;Tong,Liang
• 通讯作者: Tong,Liang