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Mycobacterium tuberculosis prokaryotic ubiquitin-like protein-deconjugating enzyme is an unusual aspartate amidase.

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.

SUBMITTER: Burns KE

PROVIDER: S-EPMC3481346 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Mycobacterium tuberculosis prokaryotic ubiquitin-like protein-deconjugating enzyme is an unusual aspartate amidase.

Burns Kristin E KE McAllister Fiona E FE Schwerdtfeger Carsten C Mintseris Julian J Cerda-Maira Francisca F Noens Elke E EE Wilmanns Matthias M Hubbard Stevan R SR Melandri Francesco F Ovaa Huib H Gygi Steven P SP Darwin K Heran KH

The Journal of biological chemistry 20120831 44

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 inhibito ...[more]

PMID: 22942282

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