1pxv
From Proteopedia
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[[Image:1pxv.jpg|left|200px]] | [[Image:1pxv.jpg|left|200px]] | ||
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'''The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease''' | '''The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease''' | ||
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[[Category: Potempa, J.]] | [[Category: Potempa, J.]] | ||
[[Category: Rzychon, M.]] | [[Category: Rzychon, M.]] | ||
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Revision as of 02:37, 3 May 2008
The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease
Overview
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.
About this Structure
1PXV is a Protein complex structure of sequences from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 05:37:26 2008