Mycobacterial MazG Is a Novel NTP Pyrophosphohydrolase Involved in Oxidative Stress Response
Publication in refereed journal

香港中文大學研究人員

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摘要MazG nucleoside triphosphate pyrophosphohydrolase (NTP-PPase, EC 3.6.1.8) from the avirulent Mycobacterium tuberculosis H37Ra contains a spontaneous mutation on a highly conserved residue, resulting in an A219E substitution (MtMazG[A219E]). In this work, we show that mycobacterial MazG from either the virulent M. tuberculosis H37Rv (MtMazG) or the fast-growing Mycobacterium smegmatis (MsMazG) is a potent NTP-PPase capable of hydrolyzing all canonical (d) NTPs, as well as the mutagenic dUTP and 8-oxo-7,8-dihydro-2'-dGTP. However, this hydrolysis activity is diminished by the MtMazG[A219E] mutation. Moreover, deletion of mazG in M. smegmatis rendered the mycobacteria defective in response to oxidative stress. Importantly, expression of the wildtype MtMazG, but not the A219E mutant, restored cell viability under oxidative stress. Intriguingly, under oxidative stress, both the mazG-null and MtMazG[A219E]-expressing M. smegmatis strains failed to elevate relA, while retaining their ability to up-regulate sigE, suggesting a specific role for the MazGNTP-PPase activity in oxidative stress-triggered, transcriptional activation of relA. The MtMazG is a homotetramer with each subunit containing a single MazG core domain flanked by two regions, both of which are essential for NTP-PPase activity. Taken together, these results demonstrate that the mycobacterial MazG is a potent NTP-PPase and that this activity is required to maintain the full capacity of the mycobacteria to respond to oxidative stress. Our work implicates a role for the MazG activity in the virulence of M. tuberculosis.
著者Lu LD, Sun Q, Fan XY, Zhong Y, Yao YF, Zhao GP
期刊名稱Journal of Biological Chemistry
出版年份2010
月份9
日期3
卷號285
期次36
出版社American Society for Biochemistry and Molecular Biology
頁次28076 - 28085
國際標準期刊號0021-9258
電子國際標準期刊號1083-351X
語言英式英語
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY

上次更新時間 2020-18-11 於 23:44