Mycobacterium tuberculosis is a notorious pathogen that continues to threaten human health. Rv0164, an antigen of both T- and B cells conserved across mycobacteria, and MSMEG_0129, its close homolog in Mycobacterium smegmatis, are predicted members of the START domain superfamily, but their molecular function is unknown. Here, gene knockout studies demonstrate MSMEG_0129 is essential for bacterial growth, suggesting Rv0164 may be a potential drug target. The MSMEG_0129 crystal structure determined at 1.95 Å reveals a fold similar to that in polyketide aromatase/cyclases ZhuI and TcmN from Streptomyces sp. Structural comparisons and docking simulations, however, infer that MSMEG_0129 and Rv0164 are unlikely to catalyze polyketide aromatization/cyclization, but probably play an irreplaceable role during mycobacterial growth, for example, in lipid transfer during cell envelope synthesis.
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http://dx.doi.org/10.1002/1873-3468.13024 | DOI Listing |
Int J Biochem Cell Biol
July 2020
Institute of Immunology, Army Medical University, Chongqing 400038, China. Electronic address:
FEBS Lett
April 2018
School of Stomatology and Medicine, Foshan University, China.
Acta Crystallogr F Struct Biol Commun
July 2017
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
Mycobacterium tuberculosis Rv0164 has previously been identified as a human T-cell antigen that induces significant production of IFN-γ in human peripheral blood mononuclear cells. M. smegmatis MSMEG_0129 shares 59% sequence identity with Rv0164.
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