6ukd
From Proteopedia
(Difference between revisions)
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==Co-complex of S. pyogenes 10782 streptopain bound with a nitrile-based specific covalent inhibitor== | ==Co-complex of S. pyogenes 10782 streptopain bound with a nitrile-based specific covalent inhibitor== | ||
| - | <StructureSection load='6ukd' size='340' side='right'caption='[[6ukd]]' scene=''> | + | <StructureSection load='6ukd' size='340' side='right'caption='[[6ukd]], [[Resolution|resolution]] 1.59Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKD OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6ukd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_ATCC_10782 Streptococcus pyogenes ATCC 10782]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UKD FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.589Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=Q9D:benzyl+[(2S)-1-(3-nitrophenyl)-3-oxobutan-2-yl]carbamate'>Q9D</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=6ukd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukd OCA], [https://pdbe.org/6ukd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ukd RCSB], [https://www.ebi.ac.uk/pdbsum/6ukd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SPEB_STRPY SPEB_STRPY] Important streptococcal virulence factor which cleaves human fibronectin and degrades vitronectin. Also cleaves human IL1B precursor to form biologically active IL1B. Can induce apoptosis in human monocytes and epithelial cells in vitro, and reduces phagocytic activity in monocytic cells. Thus, may play a role in bacterial colonization, invasion, and inhibition of wound healing.<ref>PMID:9864206</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Members of the CA class of cysteine proteases have multifaceted roles in physiology and virulence for many bacteria. Streptococcal pyrogenic exotoxin B (SpeB) is secreted by Streptococcus pyogenes and implicated in the pathogenesis of the bacterium through degradation of key human immune effector proteins. Here, we developed and characterized a clickable inhibitor, 2S-alkyne, based on X-ray crystallographic analysis and structure-activity relationships. Our SpeB probe showed irreversible enzyme inhibition in biochemical assays and labeled endogenous SpeB in cultured S. pyogenes supernatants. Importantly, application of 2S-alkyne decreased S. pyogenes survival in the presence of human neutrophils and supports the role of SpeB-mediated proteolysis as a mechanism to limit complement-mediated host defense. We posit that our SpeB inhibitor will be a useful chemical tool to regulate, label, and quantitate secreted cysteine proteases with SpeB-like activity in complex biological samples and a lead candidate for new therapeutics designed to sensitize S. pyogenes to host immune clearance. | ||
| + | |||
| + | An Irreversible Inhibitor to Probe the Role of Streptococcus pyogenes Cysteine Protease SpeB in Evasion of Host Complement Defenses.,Woehl JL, Kitamura S, Dillon N, Han Z, Edgar LJ, Nizet V, Wolan DW ACS Chem Biol. 2020 Aug 21;15(8):2060-2069. doi: 10.1021/acschembio.0c00191. Epub, 2020 Jul 28. PMID:32662975<ref>PMID:32662975</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ukd" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Streptococcus pyogenes ATCC 10782]] | ||
[[Category: Kitamura S]] | [[Category: Kitamura S]] | ||
[[Category: Woehl JL]] | [[Category: Woehl JL]] | ||
[[Category: Wolan DW]] | [[Category: Wolan DW]] | ||
Revision as of 07:53, 11 October 2023
Co-complex of S. pyogenes 10782 streptopain bound with a nitrile-based specific covalent inhibitor
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