STRUCTURAL STUDIES OF HMG-COA SYNTHASE

HMG-COA 合成酶的结构研究

• 批准号: 7370683
• 负责人: FLORENCE POJER
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370683
• 关键词: STRUCTURAL; STUDIES; HMG; COA; SYNTHASE

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。三羟基-3-甲基戊二酰辅酶A（HMG-CoA）合酶催化类异戊二烯、胆固醇和酮体产生途径中的关键步骤。最近，细菌HMG-CoA合酶的结构被公布。我们的工作集中在真核生物HMG-CoA合酶。使用内部X射线源筛选晶体，它们显示出良好的衍射，但斑点太近而无法处理数据。然而，在ESRF同步加速器上，每0.25拍摄一次图像就可以解决这个结构，处理过程显示了一个巨大的晶胞（61 x61 x412）。我们目前的首要任务是将抑制剂的结构结合在活性位点上。已经获得了野生型以及突变型酶抑制剂复合物的晶体。巨大的单胞边缘迫使使用同步辐射。