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 PubMed
Staphostatins are the endogenous, highly specific inhibitors of staphopains, the major secreted cysteine proteases from Staphylococcus aureus. We have previously shown that staphostatins A and B are competitive, active site-directed inhibitors that span the active site clefts of their target proteases in the same orientation as substrates. We now report the crystal structure of staphostatin B in complex with wild-type staphopain B at 1.9 A resolution. In the complex structure, the catalytic residues are found in exactly the positions that would be expected for uncomplexed papain-type proteases. There is robust, continuous density for the staphostatin B binding loop and no indication for cleavage of the peptide bond that comes closest to the active site cysteine of staphopain B. The carbonyl carbon atom C of this peptide bond is 4.1 A away from the active site cysteine sulfur Sgamma atom. The carbonyl oxygen atom O of this peptide bond points away from the putative oxyanion hole and lies almost on a line from the Sgamma atom to the C atom. The arrangement is strikingly similar to the "ionmolecule" arrangement for the complex of papain-type enzymes with their substrates but differs significantly from the arrangement conventionally assumed for the Michaelis complex of papain-type enzymes with their substrates and also from the arrangement that is crystallographically observed for complexes of standard mechanism inhibitors and their target serine proteases.
A comparison of staphostatin B with standard mechanism serine protease inhibitors.,Filipek R, Potempa J, Bochtler M J Biol Chem. 2005 Apr 15;280(15):14669-74. Epub 2005 Jan 11. PMID:15644332[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rzychon M, Sabat A, Kosowska K, Potempa J, Dubin A. Staphostatins: an expanding new group of proteinase inhibitors with a unique specificity for the regulation of staphopains, Staphylococcus spp. cysteine proteinases. Mol Microbiol. 2003 Aug;49(4):1051-66. PMID:12890028
- ↑ Shaw LN, Golonka E, Szmyd G, Foster SJ, Travis J, Potempa J. Cytoplasmic control of premature activation of a secreted protease zymogen: deletion of staphostatin B (SspC) in Staphylococcus aureus 8325-4 yields a profound pleiotropic phenotype. J Bacteriol. 2005 Mar;187(5):1751-62. PMID:15716447 doi:http://dx.doi.org/187/5/1751
- ↑ Filipek R, Potempa J, Bochtler M. A comparison of staphostatin B with standard mechanism serine protease inhibitors. J Biol Chem. 2005 Apr 15;280(15):14669-74. Epub 2005 Jan 11. PMID:15644332 doi:http://dx.doi.org/M411792200
