STRUCTURAL STUDIES OF HMG-COA SYNTHASE

HMG-COA 合成酶的结构研究

• 批准号: 7721882
• 负责人: FLORENCE POJER
• 金额: $ 0.29万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721882
• 关键词: Active Sites; Binding; Cells; Cholesterol; Coenzyme A; Commit; Complex; Computer Retrieval of Information on Scientific Projects Database; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Eukaryota; Eukaryotic Cell; Funding; Grant; Housing; Image; Institution; Ketone Bodies; Pathway interactions; Process; Production; Publishing; Research; Research Personnel; Resources; Source; Spottings; Structure; Synchrotrons; United States National Institutes of Health; Work; computerized data processing; inhibitor/antagonist; isoprenoid; mutant; synchrotron radiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Three-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase catalyses a committed step in the pathways for isoprenoid, cholesterol, and ketone body production. Recently, the structure of bacterial HMG-CoA synthase was published. Our work is focused on a eukaryote HMG-CoA synthase. Crystals were screened using the in-house x-ray source, they showed a good diffraction, but the spots were too close to be able to process the data. However, the structure could be solved at the ESRF synchrotron by taking images every 0.25¿, the processing revealed a huge unit cell (61x61x412). Our current first priority is to get the structure of inhibitors bound in the active site. Crystals of wild-type, as well as mutant, enzyme-inhibitors complexes have been obtained. The huge unit cell edge forces the use of synchrotron radiation.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 三羟基-3-甲基戊二酰辅酶A(HMG-CoA)合成酶催化类异戊二烯、胆固醇和酮体生成途径中的一个关键步骤。最近，细菌HMG-CoA合成酶的结构被公布。我们的工作集中在真核生物的HMG-CoA合成酶上。使用内部X射线源对晶体进行筛选，它们显示出良好的衍射效果，但光斑太近，无法处理数据。然而，这个结构可以在ESRF同步加速器上通过每0.25°拍摄一次图像来解决，处理显示出一个巨大的单元格(61x61x412)。我们目前的首要任务是获得结合在活性部位的抑制剂的结构。已经获得了野生型和突变型酶抑制剂复合体的晶体。巨大的单位电池边缘迫使使用同步辐射。