结核分枝杆菌细胞色素 P450 系统。
The Mycobacterium tuberculosis cytochrome P450 system.
机构信息
Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
出版信息
Arch Biochem Biophys. 2010 Jan 1;493(1):82-95. doi: 10.1016/j.abb.2009.07.011. Epub 2009 Jul 25.
Abstract
Tuberculosis remains a leading cause of human mortality. The emergence of strains of Mycobacterium tuberculosis, the causative agent, that are resistant to the major frontline antitubercular drugs increases the urgency for the development of new therapeutic agents. Sequencing of the M. tuberculosis genome revealed the existence of 20 cytochrome P450 enzymes, some of which are potential candidates for drug targeting. The recent burst of studies reporting microarray-based gene essentiality and transcriptome analyses under in vitro, ex vivo and in vivo conditions highlight the importance of selected P450 isoforms for M. tuberculosis viability and pathogenicity. Current knowledge of the structural and biochemical properties of the M. tuberculosis P450 enzymes and their putative redox partners is reviewed, with an emphasis on findings related to their physiological function(s) as well as their potential as drug targets.
摘要
结核病仍然是人类死亡的主要原因。导致结核病的结核分枝杆菌菌株对主要一线抗结核药物产生耐药性，这增加了开发新治疗药物的紧迫性。结核分枝杆菌基因组测序表明，存在 20 种细胞色素 P450 酶，其中一些可能是药物靶向的候选药物。最近大量研究报告了基于微阵列的基因必需性和体外、离体和体内条件下的转录组分析，强调了选定的 P450 同工酶对结核分枝杆菌活力和致病性的重要性。本文综述了结核分枝杆菌 P450 酶的结构和生化特性及其潜在的氧化还原伴侣的现有知识，重点介绍了与它们的生理功能以及作为药物靶点的潜力相关的发现。
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