Structural insight into serine protease Rv3671c that Protects M. tuberculosis from oxidative and acidic stress.

TitleStructural insight into serine protease Rv3671c that Protects M. tuberculosis from oxidative and acidic stress.
Publication TypeJournal Article
Year of Publication2010
AuthorsBiswas T, Small J, Vandal O, Odaira T, Deng H, Ehrt S, Tsodikov OV
Date Published2010 Oct 13
KeywordsBacterial Proteins, Binding Sites, Crystallization, Cysteine, Disulfides, Electrophoresis, Polyacrylamide Gel, Hydrogen-Ion Concentration, Models, Molecular, Mutation, Mycobacterium tuberculosis, Oxidation-Reduction, Oxidative Stress, Protein Binding, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Serine Proteases, X-Ray Diffraction

Rv3671c, a putative serine protease, is crucial for persistence of Mycobacterium tuberculosis in the hostile environment of the phagosome. We show that Rv3671c is required for M. tuberculosis resistance to oxidative stress in addition to its role in protection from acidification. Structural and biochemical analyses demonstrate that the periplasmic domain of Rv3671c is a functional serine protease of the chymotrypsin family and, remarkably, that its activity increases on oxidation. High-resolution crystal structures of this protease in an active strained state and in an inactive relaxed state reveal that a solvent-exposed disulfide bond controls the protease activity by constraining two distant regions of Rv3671c and stabilizing it in the catalytically active conformation. In vitro biochemical studies confirm that activation of the protease in an oxidative environment is dependent on this reversible disulfide bond. These results suggest that the disulfide bond modulates activity of Rv3671c depending on the oxidative environment in vivo.

Alternate JournalStructure
PubMed ID20947023
PubMed Central IDPMC2955984
Grant ListR01 AI081725 / AI / NIAID NIH HHS / United States
R0I AI081725 / AI / NIAID NIH HHS / United States

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