以酪蛋白水解蛋白酶P及其AAA1伴侣蛋白为靶点用于结核病治疗。
Targeting caseinolytic protease P and its AAA1 chaperone for tuberculosis treatment.
作者信息
Xu Xin, Zhang Laiying, Yang Tao, Qiu Zhiqiang, Bai Lang, Luo Youfu
机构信息
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Laboratory of Human Diseases and Immunotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
出版信息
Drug Discov Today. 2023 Mar;28(3):103508. doi: 10.1016/j.drudis.2023.103508. Epub 2023 Jan 24.
Caseinolytic protease P with its AAA1 chaperone, known as Mycobacterium tuberculosis (Mtb)ClpP1P2 proteolytic machinery, maintains protein homeostasis in Mtb cells and is essential for bacterial survival. It is regarded as an important biological target with the potential to address the increasingly serious issue of multidrug-resistant (MDR) TB. Over the past 10 years, many MtbClpP1P2-targeted modulators have been identified and characterized, some of which have shown potent anti-TB activity. In this review, we describe current understanding of the substrates, structure and function of MtbClpP1P2, classify the modulators of this important protein machine into several categories based on their binding subunits or pockets, and discuss their binding details; Such information provides insights for use in candidate drug research and development of TB treatments by targeting MtbClpP1P2 proteolytic machinery.
酪蛋白水解蛋白酶P及其AAA1伴侣（即结核分枝杆菌（Mtb）的ClpP1P2蛋白水解机制）维持Mtb细胞中的蛋白质稳态，对细菌存活至关重要。它被视为一个重要的生物学靶点，有可能解决日益严重的耐多药（MDR）结核病问题。在过去10年中，许多靶向MtbClpP1P2的调节剂已被鉴定和表征，其中一些已显示出强大的抗结核活性。在本综述中，我们描述了目前对MtbClpP1P2的底物、结构和功能的理解，根据其结合亚基或口袋将这种重要蛋白质机器的调节剂分为几类，并讨论它们的结合细节；这些信息为通过靶向MtbClpP1P2蛋白水解机制进行结核病治疗的候选药物研发提供了见解。
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