1PXV: The Staphostatin-Staphopain Complex: A Forward Binding Inhibitor In Complex With Its Target Cysteine Protease

Staphostatins are the endogenous inhibitors of the major secreted cysteine proteases of Staphylococcus aureus, the staphopains. Our recent crystal structure of staphostatin B has shown that this inhibitor forms a mixed, eight-stranded beta-barrel with statistically significant similarity to lipocalins, but not to cystatins. We now present the 1.8-A crystal structure of staphostatin B in complex with an inactive mutant of its target protease. The complex is held together through extensive interactions and buries a total surface area of 2300 A2. Unexpectedly for a cysteine protease inhibitor, staphostatin B binds to staphopain B in an almost substrate-like manner. The inhibitor polypeptide chain runs through the protease active site cleft in the forward direction, with residues IG-TS in P2 to P2' positions. Both in the free and complexed forms, the P1 glycine residue of the inhibitor is in a main chain conformation only accessible to glycines. Mutations in this residue lead to a loss of affinity of the inhibitor for protease and convert the inhibitor into a substrate.
PDB ID: 1PXVDownload
MMDB ID: 25081
PDB Deposition Date: 2003/7/7
Updated in MMDB: 2003/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 1PXV: dimeric; determined by author and by software (PISA)
Molecular Components in 1PXV
Label Count Molecule
Proteins (2 molecules)
Cysteine Protease
Molecule annotation
Cysteine Protease Inhibitor(Gene symbol: SAOUHSC_00986)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB