Rv0132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent hydroxymycolic acid dehydrogenase.
Rv0132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent hydroxymycolic acid dehydrogenase.
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DOI：
10.1371/journal.pone.0081985
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mukhopadhyay B
中科院分区：
文献类型：
--
作者：
Purwantini E;Mukhopadhyay B
结核分枝杆菌操纵和逃避人类免疫系统的能力部分归因于其异常复杂的细胞壁。该细胞壁的关键成分之一是称为分枝菌酸的脂质家族。分枝菌酸的氧化产生甲氧基和酮分枝菌酸，增强了结核分枝杆菌的致病特性。因此，各个酶在分枝杆菌的研究中很有意义。甲氧基和酮菌酸的产生是通过羟基霉菌酸的中间形成而进行的。虽然从羟基分枝菌酸生成甲氧基分枝菌酸的甲基转移酶是已知的，但将羟基分枝菌酸氧化成酮分枝菌酸的羟基分枝菌酸脱氢酶一直难以捉摸。我们发现羟基霉菌酸脱氢酶由rv0132c基因编码，该酶利用脱氮黄素辅酶F420作为电子载体，因此我们将其称为F420依赖性羟基霉菌酸脱氢酶。这是关于 F420 参与分枝杆菌细胞包膜合成的第一份报告。此外，F420依赖性羟基霉菌酸脱氢酶被PA-824抑制，因此，它是这种新结核病药物以前未知的靶点。
The ability of Mycobacterium tuberculosis to manipulate and evade human immune system is in part due to its extraordinarily complex cell wall. One of the key components of this cell wall is a family of lipids called mycolic acids. Oxygenation of mycolic acids generating methoxy- and ketomycolic acids enhances the pathogenic attributes of M. tuberculosis. Thus, the respective enzymes are of interest in the research on mycobacteria. The generation of methoxy- and ketomycolic acids proceeds through intermediary formation of hydroxymycolic acids. While the methyl transferase that generates methoxymycolic acids from hydroxymycolic acids is known, hydroxymycolic acids dehydrogenase that oxidizes hydroxymycolic acids to ketomycolic acids has been elusive. We found that hydroxymycolic acid dehydrogenase is encoded by the rv0132c gene and the enzyme utilizes F420, a deazaflavin coenzyme, as electron carrier, and accordingly we called it F420-dependent hydroxymycolic acid dehydrogenase. This is the first report on the involvement of F420 in the synthesis of a mycobacterial cell envelope. Also, F420-dependent hydroxymycolic acid dehydrogenase was inhibited by PA-824, and therefore, it is a previously unknown target for this new tuberculosis drug.
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