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Discovery of anti-TB agents that target the cell-division protein FtsZ

机译:发现靶向细胞分裂蛋白FtsZ的抗结核病药物

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摘要

The emergence of multidrug-resistant Mycobacterium tuberculosis strains has made many of the currently available anti-tuberculosis (TB) drugs ineffective. Accordingly, there is a pressing need to identify new drug targets. Filamentous temperature-sensitive protein Z (FtsZ), a bacterial tubulin homologue, is an essential cell-division protein that polymerizes in a GTP-dependent manner, forming a highly dynamic cytokinetic ring, designated as the Z ring, at the septum site. Other cell-division proteins are recruited to the Z ring and, upon resolution of the septum, two daughter cells are produced. Since inactivation of FtsZ or alteration of FtsZ assembly results in the inhibition of Z-ring and septum formation, FtsZ is a very promising target for novel antimicrobial drug development. This review describes the function and dynamic behaviors of FtsZ and the recent development of FtsZ inhibitors as potential anti-TB agents.
机译:耐多药结核分枝杆菌菌株的出现使许多目前可用的抗结核药无效。因此,迫切需要鉴定新的药物靶标。丝状温度敏感蛋白Z(FtsZ)是细菌微管蛋白的同源物,是一种必需的细胞分裂蛋白,它以GTP依赖性方式聚合,在隔膜部位形成高度动态的细胞动力学环,称为Z环。其他细胞分裂蛋白被募集到Z环,并且在隔片分离后,产生了两个子细胞。由于FtsZ的失活或FtsZ装配的改变导致Z环和隔垫的形成受到抑制,因此FtsZ是新型抗菌药物开发的非常有希望的目标。这篇综述描述了FtsZ的功能和动态行为以及作为潜在抗结核病药物的FtsZ抑制剂的最新发展。

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