Structural and genetic analysis of START START superfamily protein MSMEG MSMEG _0129 from Mycobacterium?smegmatis Mycobacterium?smegmatis

摘要

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?? 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.