LOOP MOVEMENT OF E COLI DIHYDROOROTASE

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来源获得了主要资金，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。酶的结构域的运动可能对它们的活性至关重要。通常，这些结构域具有不同的构象，这取决于酶的催化状态。因此，研究酶在构象状态下的结构对于理解酶催化和抑制剂设计至关重要。二氢乳清酸酶（DHOase）是一种锌金属酶，在嘧啶从头合成的第三步中催化N-氨甲酰基-L-天冬氨酸可逆环化为L-二氢乳清酸。在最近测定的E. coli DHOase（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。我们已经产生了一系列定点突变体，以探讨这些运动的作用，

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