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结核分枝杆菌半胱氨酰转移酶 mycothiol 连接酶对 tRNA 合成酶抑制剂的敏感性和结合模式。

Susceptibility and mode of binding of the Mycobacterium tuberculosis cysteinyl transferase mycothiol ligase to tRNA synthetase inhibitors.

机构信息

Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States.

出版信息

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2480-3. doi: 10.1016/j.bmcl.2011.02.042. Epub 2011 Feb 17.

Abstract

The cysteinyl transferase mycothiol ligase, or MshC, catalyzes the fourth step in the biosynthesis of the small molecular weight thiol mycothiol. MshC is essential for growth of Mycobacterium tuberculosis. Two groups of known aminoacyl tRNA synthetase inhibitors were evaluated for inhibition of M. tuberculosis MshC including aminoacyl adenosine analogs and natural products. Using enzyme assays, isothermal titration calorimetry and NMR, we show that MshC is selectively inhibited by cysteinyl sulfamoyl adenosine, and that discrimination occurs at the amino acid moiety.

摘要

半胱氨酰转移酶巯基乙硫醇连接酶(MshC)催化小分子巯基乙硫醇生物合成的第四步。MshC 是结核分枝杆菌生长所必需的。评估了两组已知的氨酰基 tRNA 合成酶抑制剂对结核分枝杆菌 MshC 的抑制作用,包括氨酰基腺苷类似物和天然产物。通过酶测定、等温滴定量热法和 NMR,我们表明 MshC 被半胱氨酰磺酰胺腺苷选择性抑制,并且区分发生在氨基酸部分。

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