炭疽芽孢杆菌二氢乳清酸酶在2.6埃分辨率下的结构。
Structure of dihydroorotase from Bacillus anthracis at 2.6 Å resolution.
作者信息
Mehboob Shahila, Mulhearn Debbie C, Truong Kent, Johnson Michael E, Santarsiero Bernard D
机构信息
Center for Pharmaceutical Biotechnology and the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, MC-870, 900 South Ashland Avenue, Chicago, IL 60607-7173, USA.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Nov 1;66(Pt 11):1432-5. doi: 10.1107/S1744309110037085. Epub 2010 Oct 27.
Abstract
Dihydroorotase (EC 3.5.2.3) catalyzes the reversible cyclization of N-carbamoyl-L-aspartate to L-dihydroorotate in the third step of the pyrimidine-biosynthesis pathway in Bacillus anthracis. A comparison is made between the structures of dihydroorotase from four different organisms, including B. anthracis dihydroorotase, and reveals substantial variations in the active site, dimer interface and overall tertiary structure. These differences demonstrate the utility of exploring multiple structures of a molecular target as expressed from different organisms and how these differences can be exploited for structure-based drug discovery.
摘要
二氢乳清酸酶（EC 3.5.2.3）在炭疽芽孢杆菌嘧啶生物合成途径的第三步中催化N-氨甲酰-L-天冬氨酸可逆环化生成L-二氢乳清酸。对来自四种不同生物体的二氢乳清酸酶结构进行了比较，包括炭疽芽孢杆菌二氢乳清酸酶，结果显示活性位点、二聚体界面和整体三级结构存在显著差异。这些差异证明了探索不同生物体表达的分子靶点的多种结构的实用性，以及如何利用这些差异进行基于结构的药物发现。
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