Abstract
Synthesis and evaluation of a chemical library of inhibitors of the mycothiol biosynthesis enzyme GlcNAc-Ins deacetylase (MshB) and the mycothiol-dependent detoxification enzyme mycothiol- S-conjugate amidase (MCA) from Mycobacterium tuberculosis are reported. The library was biased to include structural features of a group of natural products previously shown to competitively inhibit MCA. Molecular docking studies that reproducibly placed the inhibitors in the active site of the enzyme MshB reveal the mode of binding and are consistent with observed biological activity.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Amidohydrolases / antagonists & inhibitors*
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Amidohydrolases / chemistry
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / chemistry
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Binding Sites
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Cysteine / metabolism*
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Furans / chemical synthesis
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Furans / chemistry
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Glycopeptides / metabolism*
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Inositol / metabolism*
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Isoxazoles / chemical synthesis
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Isoxazoles / chemistry
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Models, Molecular
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Mycobacterium tuberculosis / enzymology*
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Oxazines / chemical synthesis
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Oxazines / chemistry
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Oxazoles / chemical synthesis
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Oxazoles / chemistry
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Protein Binding
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Pyrans / chemical synthesis
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Pyrans / chemistry
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Stereoisomerism
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Thioglycosides / chemical synthesis*
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Thioglycosides / chemistry
Substances
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Bacterial Proteins
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Furans
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Glycopeptides
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Isoxazoles
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Oxazines
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Oxazoles
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Pyrans
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Sulfonamides
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Thioglycosides
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mycothiol
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Inositol
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Amidohydrolases
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N-acetyl-1-D-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase
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mycothiol S-conjugate amidase
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Cysteine