Abstract
Deamidase of Pup (Dop), the prokaryotic ubiquitin-like protein (Pup)-deconjugating enzyme, is critical for the full virulence of Mycobacterium tuberculosis and is unique to bacteria, providing an ideal target for the development of selective chemotherapies. We used a combination of genetics and chemical biology to characterize the mechanism of depupylation. We identified an aspartate as a potential nucleophile in the active site of Dop, suggesting a novel protease activity to target for inhibitor development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amidohydrolases / chemistry*
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Amidohydrolases / genetics
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Amino Acid Motifs
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Amino Acid Sequence
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Amino Acid Substitution
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Biocatalysis
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Catalytic Domain
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Diazooxonorleucine / chemistry
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Enzyme Inhibitors / chemistry
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Hydrolysis
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Mycobacterium tuberculosis / enzymology*
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Structural Homology, Protein
Substances
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Bacterial Proteins
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Enzyme Inhibitors
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Diazooxonorleucine
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Amidohydrolases