5a0r
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Product peptide-bound structure of metalloprotease Zmp1 variant E143A from Clostridium difficile== | |
| + | <StructureSection load='5a0r' size='340' side='right'caption='[[5a0r]], [[Resolution|resolution]] 1.25Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5a0r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A0R 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]] 1.251Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5a0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a0r OCA], [https://pdbe.org/5a0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a0r RCSB], [https://www.ebi.ac.uk/pdbsum/5a0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a0r ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PPEP1_CLOD6 PPEP1_CLOD6] Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin.<ref>PMID:24303041</ref> <ref>PMID:24623589</ref> <ref>PMID:26283789</ref> <ref>PMID:26522134</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. In common with other pathogenic bacteria, C. difficile secretes proteins involved in adhesion, colonization, and dissemination. The recently identified Zmp1 is an extracellular metalloprotease showing a unique specificity for Pro-Pro peptide bonds. The endogenous substrates of Zmp1 are two surface proteins implicated in adhesion of C. difficile to surface proteins of human cells. Thus, Zmp1 is believed to be involved in the regulation of the adhesion-motility balance of C. difficile. Here, we report crystal structures of Zmp1 from C. difficile in its unbound and peptide-bound forms. The structure analysis revealed a fold similar to Bacillus anthracis lethal factor. Crystal structures in the open and closed conformation of the S-loop shed light on the mode of binding of the substrate, and reveal important residues for substrate recognition and the strict specificity of Zmp1 for Pro-Pro peptide bonds. | ||
| - | + | Structural Basis of Proline-Proline Peptide Bond Specificity of the Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile.,Schacherl M, Pichlo C, Neundorf I, Baumann U Structure. 2015 Jul 21. pii: S0969-2126(15)00271-3. doi:, 10.1016/j.str.2015.06.018. PMID:26211609<ref>PMID:26211609</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5a0r" style="background-color:#fffaf0;"></div> |
| - | [[Category: Baumann | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: Pichlo | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Clostridioides difficile 630]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Baumann U]] | ||
| + | [[Category: Neundorf I]] | ||
| + | [[Category: Pichlo C]] | ||
| + | [[Category: Schacherl M]] | ||
Current revision
Product peptide-bound structure of metalloprotease Zmp1 variant E143A from Clostridium difficile
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