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.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / pharmacology
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Amino Acid Sequence
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Amino Acyl-tRNA Synthetases / antagonists & inhibitors*
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Amino Acyl-tRNA Synthetases / metabolism
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism
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Biological Products / chemistry
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Biological Products / pharmacology
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Ligases / antagonists & inhibitors*
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Ligases / metabolism
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Molecular Sequence Data
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Mycobacterium tuberculosis / enzymology*
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Protein Binding
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Sequence Alignment
Substances
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Bacterial Proteins
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Biological Products
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Ligases
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Amino Acyl-tRNA Synthetases
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Adenosine