High Flux X-ray Crystallography Data Collection System

高通量 X 射线晶体学数据采集系统

• 批准号: 6739509
• 负责人: HARLAN Tonie WRIGHT
• 金额: $ 50万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739509
• 关键词: X ray crystallography; bioimaging /biomedical imaging; biomedical equipment purchase; macromolecule; structural biology

DESCRIPTION (provided by applicant): This proposal requests funds for an x-ray diffraction data collection system consisting of a high intensity rotating anode x-ray source with focusing mirrors, image plate detector, cryocooling accessory and computer to be used in biological macromolecule structure determination in a number of studies in our laboratories. This instrument will serve a community of macromolecule crystallographers and their collaborators, most of whom are housed in the Institute of Structural Biology and Drug Discovery of Virginia Commonwealth University. The structural studies to be carried out with this instrument are all coordinated with broad projects of basic, biomedical significance drawing on the skills of biochemists, molecular biologists and medicinal chemists as well as crystallographers. These studies include: enzymes of fatty acid biosynthesis and intermediary metabolism, which are targets for new drug discovery in such diseases as tuberculosis; enzymes of pyridoxal phosphate and folate metabolism that are potential targets for new cancer chemotherapeutic agents and cardiovascular treatment; development of anti-sickling agents for sickle cell hemoglobin; serpins and their complexes with heparin and other ligands, which play critical roles in fibrinolysis, thrombosis and Alzheimer's disease; RNA methylases, which are new potential drug targets in infectious diseases; and pathogenic bacterial transcriptional factors. The determination of macromolecule structures is an essential component of these projects and is carried out by a team of 6 experienced x-ray crystallographers. The instrument for which funds are requested will replace a 15 year old x-ray diffraction data collection system that has been in continuous and heavy use throughout that period and which is now suffering frequent failures with consequent delays in structure determination and disruptions of the research projects for which those structures are required. The instrument will be housed and maintained in the Institute of Structural Biology and Drug Discovery, to which Virginia Commonwealth University has made a long term commitment of provision of infrastructure and maintenance support.

描述（由申请人提供）： 该提案请求资金用于X射线衍射数据收集系统，该系统由带聚焦镜的高强度旋转阳极X射线源、图像板探测器、低温冷却附件和计算机组成，用于我们实验室的许多研究中的生物大分子结构测定。该仪器将为大分子晶体学家及其合作者社区提供服务，其中大多数人都在弗吉尼亚联邦大学结构生物学和药物发现研究所。利用该仪器进行的结构研究均与利用生物化学家、分子生物学家、药物化学家以及晶体学家的技能的具有基础生物医学意义的广泛项目相协调。这些研究包括：脂肪酸生物合成和中间代谢酶，它们是结核病等疾病新药发现的目标；磷酸吡哆醛和叶酸代谢酶是新型癌症化疗药物和心血管治疗的潜在靶点；开发镰状细胞血红蛋白抗镰状化剂；丝氨酸蛋白酶抑制剂及其与肝素和其他配体的复合物，在纤维蛋白溶解、血栓形成和阿尔茨海默病中发挥着关键作用； RNA甲基化酶，是传染病中新的潜在药物靶点；和致病细菌转录因子。大分子结构的测定是这些项目的重要组成部分，由 6 名经验丰富的 X 射线晶体学家组成的团队进行。申请资金的仪器将取代已有 15 年历史的 X 射线衍射数据收集系统，该系统在此期间一直持续大量使用，目前经常出现故障，从而导致结构测定的延迟和需要这些结构的研究项目的中断。该仪器将在结构生物学和药物发现研究所安置和维护，弗吉尼亚联邦大学已长期承诺提供基础设施和维护支持。