1pxv: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| (12 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease== | ||
<StructureSection load='1pxv' size='340' side='right'caption='[[1pxv]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1pxv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PXV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pxv OCA], [https://pdbe.org/1pxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pxv RCSB], [https://www.ebi.ac.uk/pdbsum/1pxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pxv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SSPB_STAAU 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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | 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. | ||
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<ref>PMID:12874290</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1pxv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Proteinase 3D structures|Proteinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Bochtler | [[Category: Bochtler M]] | ||
[[Category: Dubin | [[Category: Dubin A]] | ||
[[Category: Filipek | [[Category: Filipek R]] | ||
[[Category: Gruca | [[Category: Gruca M]] | ||
[[Category: Oleksy | [[Category: Oleksy A]] | ||
[[Category: Potempa | [[Category: Potempa J]] | ||
[[Category: Rzychon | [[Category: Rzychon M]] | ||
Latest revision as of 11:24, 2 August 2023
The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease
| ||||||||||||
