3K6Y: Crystal Structure Of Rv3671c Protease From M. Tuberculosis, Active Form

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.
PDB ID: 3K6YDownload
MMDB ID: 85453
PDB Deposition Date: 2009/10/10
Updated in MMDB: 2010/11
Experimental Method:
x-ray diffraction
Resolution: 1.3  Å
Source Organism:
Similar Structures:
Biological Unit for 3K6Y: dimeric; determined by author and by software (PISA)
Molecular Components in 3K6Y
Label Count Molecule
Proteins (2 molecules)
Possible Membrane-associated Serine Protease
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB