酶
色氨酸合酶
肺结核
机制(生物学)
催化作用
色氨酸
化学
组合化学
ATP合酶
药物靶点
药品
生物化学
立体化学
计算生物学
生物
药理学
医学
物理
氨基酸
病理
量子力学
作者
Carla S. S. Teixeira,María J. Ramos,Sérgio F. Sousa,Nuno M. F. S. A. Cerqueira
出处
期刊:Chemcatchem
[Wiley]
日期:2019-10-22
卷期号:12 (1): 227-237
被引量:9
标识
DOI:10.1002/cctc.201901505
摘要
Abstract Tryptophan Synthase (TSase) is an emergent therapeutic target in the treatment of tuberculosis. Interest in TSase as a drug target arose from the fact that this enzyme is not present in humans, while in bacteria, like M. tuberculosis , it catalyses the last two steps in the tryptophan biosynthetic pathway. Several inhibitors of TSase have recently been developed, with promising results. However, the exact catalytic mechanism of this enzyme has remained unexplained at the atomic level. The fact that TSase is a multifunctional enzyme, with two dimers, each one with two independent active sites, interconnected by a 25 Å tunnel, has made it a challenging enzyme, from the catalytic point of view. QM/MM calculations were used to analyze and explain the two steps catalyzed by this enzyme. The results provide an atomic‐level clarification of the full catalytic mechanism of this enzyme, offering also important clues for the development of new inhibitors against tuberculosis.
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