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新型抗结核药物靶标的寻找与验证是抗结核新药发现的关键环节。近期研究发现,结核分枝杆菌编码表达20余种细胞色素P450酶(CYP450s)。这些CYP450s在活跃或潜伏期结核分枝杆菌(Mtb)的脂质代谢与合成、胆固醇利用、呼吸链电子传递等方面扮演十分重要的角色。目前6个亚型的蛋白质晶体结构已被阐明,提示其具有成为抗结核药物靶标的潜力。本文将结合最新发表的文献,主要从Mtb CYP450酶系同源性、各亚型结构与功能、与唑类等小分子抑制剂相互作用机制等角度,总结该类蛋白可靶性的依据,为进一步的抗结核药物筛选与设计提供参考。
The search and verification of new anti-TB drug targets are the key links in the discovery of new anti-TB drugs. Recent studies have found that M. tuberculosis encodes more than 20 cytochrome P450 enzymes (CYP450s). These CYP450s play an important role in the lipid metabolism and synthesis of active and latent Mtb, cholesterol utilization, and respiratory chain electron transport. The crystal structures of the six subtypes have now been elucidated, suggesting their potential as targets for anti-TB drugs. In this review, we will summarize the basis for the target-specific properties of Mtb CYP450 from the perspective of the homology of Mtb CYP450 enzymes, the structure and function of each subtype, the interaction with small molecule inhibitors such as azoles, etc. Further anti-TB drug screening and design provide a reference.