1pxv
From Proteopedia
The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease
Structural highlights
Function[SSPB_STAAU] Cysteine protease able to degrade elastin, fibrogen, fibronectin and kininogen. Exhibits a strong preference for substrates where arginine is preceded by a hydrophobic amino acid. Promotes detachment of primary human keratinocytes. Along with other extracellular proteases is involved in colonization and infection of human tissues (By similarity). [SSPC_STAA8] Specifically inhibits the cysteine protease staphopain B (SspB) by blocking the active site of the enzyme. Probably required to protect cytoplasmic proteins from being degraded by prematurely activated/folded prostaphopain B. Also involved in growth capacity, viability and bacterial morphology.[1] [2] Publication Abstract from PubMedStaphostatins 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. The Staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease.,Filipek R, Rzychon M, Oleksy A, Gruca M, Dubin A, Potempa J, Bochtler M J Biol Chem. 2003 Oct 17;278(42):40959-66. Epub 2003 Jul 21. PMID:12874290[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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