LOOP MOVEMENT OF E COLI DIHYDROOROTASE

大肠杆菌二氢乳清酶的循环运动

• 批准号: 7370703
• 负责人: J MITCHELL GUSS
• 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/7370703
• 关键词: LOOP; MOVEMENT; COLI; DIHYDROOROTASE

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. Movements of structural domains of enzymes can be critical to their activity. Generally these domains have different conformations depending on the catalytic state of the enzyme. Therefore, the study of the structures of enzymes in conformational states is critical to understanding the enzyme catalysis and inhibitor design. Dihydroorotase (DHOase) is a zinc metalloenzyme that catalyzes the reversible cyclization of N-carbamyl-L- aspartate to L-dihydroorotate in the third step of de novo pyrimidine synthesis. In a recently determined structure of E. coli DHOase (Lee et al. (2005), J Mol Biol, 348, 523-533), we observed two different conformations of a loop comprised of residues 105-115. These conformations may be tightly linked to the catalytic state of DHOase. We have generated a series of site-directed mutants to probe the role of these moveme

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。酶结构域的运动对其活性至关重要。一般来说，这些结构域根据酶的催化状态具有不同的构象。因此，构象态酶结构的研究对于理解酶催化和抑制剂设计至关重要。二氢乳清酶 (DHOase) 是一种锌金属酶，在嘧啶从头合成的第三步中催化 N-氨甲酰-L-天冬氨酸可逆环化为 L-二氢乳清酸。在最近确定的大肠杆菌 DHOase 结构中（Lee 等人 (2005), J Mol Biol, 348, 523-533），我们观察到由残基 105-115 组成的环的两种不同构象。这些构象可能与 DHOase 的催化状态紧密相关。我们已经生成了一系列定点突变体来探究这些 moveme 的作用