LOOP MOVEMENT OF E COLI DIHYDROOROTASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。酶结构域的运动对酶的活性至关重要。通常这些结构域根据酶的催化状态有不同的构象。因此，研究酶在构象状态下的结构对于理解酶的催化作用和抑制剂的设计至关重要。二氢羊角酸酶（DHOase）是一种锌金属酶，在重新合成嘧啶的第三步催化n -氨甲酰- l-天冬氨酸可逆环化成l-二氢羊角酸。在最近确定的大肠杆菌hoase结构中（Lee et al. (2005), J Mol Biol, 348, 523-533），我们观察到由残基105-115组成的环有两种不同的构象。这些构象可能与氧化酶的催化状态密切相关。我们已经生成了一系列的位点导向突变体来探索这些运动的作用

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