2n6j

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==Solution structure of Zmp1, a zinc-dependent metalloprotease secreted by Clostridium difficile==
==Solution structure of Zmp1, a zinc-dependent metalloprotease secreted by Clostridium difficile==
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<StructureSection load='2n6j' size='340' side='right'caption='[[2n6j]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2n6j' size='340' side='right'caption='[[2n6j]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2n6j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N6J FirstGlance]. <br>
<table><tr><td colspan='2'>[[2n6j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N6J FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">zmp1, CD630_28300 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272563 Clostridioides difficile 630])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=2n6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n6j OCA], [https://pdbe.org/2n6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n6j RCSB], [https://www.ebi.ac.uk/pdbsum/2n6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n6j ProSAT]</span></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=2n6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n6j OCA], [https://pdbe.org/2n6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n6j RCSB], [https://www.ebi.ac.uk/pdbsum/2n6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n6j ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/ZMP1_PEPD6 ZMP1_PEPD6]] Zinc-dependent endoprotease with a preference for proline residues surrounding the scissile bond. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites. 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 have a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins, and 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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Proteases are commonly secreted by microorganisms. In some pathogens, they can play a series of functional roles during infection, including maturation of cell surface or extracellular virulence factors, interference with host cell signaling, massive host tissue destruction, and dissolution of infection-limiting clots through degradation of the host proteins devoted to the coagulation cascade. We previously reported the identification and characterization of Zmp1, a zinc-dependent metalloprotease secreted by Clostridium difficile, demonstrated that Zmp1 is able to degrade fibrinogen in vitro, and identified two residues necessary to the catalytic activity. In the present work, we solved the solution structure of Zmp1 by Nuclear Magnetic Resonance (NMR) and compared it with the recently solved X-ray structures of substrate-bound and substrate-free Zmp1, highlighting similarities and differences. We also combined the structural characterization to biochemical assays and site-directed mutagenesis, to provide new insights into the catalytic site and on the residues responsible for substrate specificity. The Zmp1 structure showed similarity to the catalytic domain of Anthrax Lethal Factor of Bacillus anthracis. Analogies and differences in the catalytic and in the substrate-binding sites of the two proteins are discussed.
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Structural characterization of zinc-bound Zmp1, a zinc-dependent metalloprotease secreted by Clostridium difficile.,Rubino JT, Martinelli M, Cantini F, Castagnetti A, Leuzzi R, Banci L, Scarselli M J Biol Inorg Chem. 2015 Dec 28. PMID:26711661<ref>PMID:26711661</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2n6j" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
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[[Category: Clostridioides difficile 630]]
[[Category: Clostridioides difficile 630]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Banci, L]]
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[[Category: Banci L]]
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[[Category: Cantini, F]]
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[[Category: Cantini F]]
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[[Category: Martinelli, M]]
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[[Category: Martinelli M]]
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[[Category: Rubino, J T]]
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[[Category: Rubino JT]]
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[[Category: Scarselli, M]]
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[[Category: Scarselli M]]
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[[Category: Hydrolase]]
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[[Category: Metalloprotease]]
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[[Category: Vaccine]]
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Current revision

Solution structure of Zmp1, a zinc-dependent metalloprotease secreted by Clostridium difficile

PDB ID 2n6j

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