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结核分枝杆菌基因组中细胞色素P450的优势情况。

The preponderance of P450s in the Mycobacterium tuberculosis genome.

作者信息

McLean Kirsty J, Clift Daniel, Lewis D Geraint, Sabri Muna, Balding Philip R, Sutcliffe Michael J, Leys David, Munro Andrew W

机构信息

Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science and School of Life Sciences, University of Manchester, Jackson's Mill, Sackville Street, Manchester, UK, M60 1QD.

出版信息

Trends Microbiol. 2006 May;14(5):220-8. doi: 10.1016/j.tim.2006.03.002. Epub 2006 Apr 3.

Abstract

The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome P450 enzymes (P450s). P450s are mono-oxygenases, which are historically considered to facilitate prokaryotic usage of unusual carbon sources. However, their preponderance in Mtb strongly indicates crucial physiological functions, as does the fact that polycyclic azoles (known P450 inhibitors) have potent anti-mycobacterial effects. Recent structural and enzyme characterization data reveal novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis, knockout studies and structural comparisons signify important roles in cell biology and pathogenesis for various P450s and redox partner enzymes in Mtb. Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen.

摘要

结核分枝杆菌(Mtb)的基因组编码20种不同的细胞色素P450酶(P450s)。P450s是单加氧酶,历史上认为其有助于原核生物利用特殊碳源。然而,它们在结核分枝杆菌中占主导地位强烈表明其具有关键的生理功能,多环唑类(已知的P450抑制剂)具有强大的抗分枝杆菌作用这一事实也说明了这一点。最近的结构和酶特性数据揭示了至少两种结核分枝杆菌P450s(CYP121和CYP51)的新特征。基因组分析、基因敲除研究和结构比较表明,各种P450s和氧化还原伴侣酶在结核分枝杆菌的细胞生物学和发病机制中具有重要作用。阐明其结构、功能和代谢作用对于将P450s作为这种主要人类病原体的“阿喀琉斯之踵”进行靶向研究至关重要。

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