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

Citation:
Abstract
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)
1
Cysteine Protease
Molecule annotation
1
Cysteine Protease Inhibitor(Gene symbol: SAOUHSC_00986)
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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