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

Tapan Biswas, Jennifer Small, Omar Vandal, Toshiko Odaira, Haiteng Deng, Sabine Ehrt, Oleg V. Tsodikov

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish
Pages (from-to)1353-1363
Number of pages11
Issue number10
StatePublished - Oct 13 2010

Bibliographical note

Funding Information:
We thank Eli Eisman for technical assistance with crystallization of Rv3671c_161-397, Dirk Schnappinger, Carl Nathan, and Evette Radisky for helpful comments and Spencer Anderson and the staff of sector LS-CAT of the Advanced Photon Source at the Argonne National Laboratory for assistance with the collection of the diffraction data. This work was funded by National Institutes of Health (ROI AI081725 to S.E.). The Department of Microbiology and Immunology acknowledges the support of the William Randolph Hearst Foundation.

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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