Abstract
We report a promising NDM-1 inhibitor, disulfiram, which can covalently bind to NDM-1 by forming an S-S bond with the Cys208 residue. Its copper-containing metabolite in vivo, Cu(DTC)2, also inactivated NDM-1 through oxidizing the Zn(ii) thiolate site of the enzyme, therefore exhibiting dual functional inhibitory potential against B1 and B2 subclass MβLs.
MeSH terms
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Disulfiram / chemistry
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Disulfiram / pharmacology*
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Escherichia coli Proteins / antagonists & inhibitors*
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Escherichia coli Proteins / metabolism
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Models, Molecular
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Molecular Structure
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beta-Lactamase Inhibitors / chemistry
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beta-Lactamase Inhibitors / pharmacology*
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beta-Lactamases / metabolism
Substances
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Escherichia coli Proteins
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beta-Lactamase Inhibitors
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NDM-1 protein, E coli
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beta-Lactamases
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Disulfiram