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5a0r

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Current revision

Product peptide-bound structure of metalloprotease Zmp1 variant E143A from Clostridium difficile

Structural highlights

5a0r is a 4 chain structure with sequence from Clostridioides difficile 630 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.251Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cafardi V, Biagini M, Martinelli M, Leuzzi R, Rubino JT, Cantini F, Norais N, Scarselli M, Serruto D, Unnikrishnan M. Identification of a novel zinc metalloprotease through a global analysis of Clostridium difficile extracellular proteins. PLoS One. 2013 Nov 26;8(11):e81306. doi: 10.1371/journal.pone.0081306., eCollection 2013. PMID:24303041 doi:http://dx.doi.org/10.1371/journal.pone.0081306
↑ Hensbergen PJ, Klychnikov OI, Bakker D, van Winden VJ, Ras N, Kemp AC, Cordfunke RA, Dragan I, Deelder AM, Kuijper EJ, Corver J, Drijfhout JW, van Leeuwen HC. A novel secreted metalloprotease (CD2830) from Clostridium difficile cleaves specific proline sequences in LPXTG cell surface proteins. Mol Cell Proteomics. 2014 May;13(5):1231-44. doi: 10.1074/mcp.M113.034728. Epub, 2014 Mar 12. PMID:24623589 doi:http://dx.doi.org/10.1074/mcp.M113.034728
↑ Peltier J, Shaw HA, Couchman EC, Dawson LF, Yu L, Choudhary JS, Kaever V, Wren BW, Fairweather NF. Cyclic diGMP regulates production of sortase substrates of Clostridium difficile and their surface exposure through ZmpI protease-mediated cleavage. J Biol Chem. 2015 Oct 2;290(40):24453-69. doi: 10.1074/jbc.M115.665091. Epub 2015, Aug 17. PMID:26283789 doi:http://dx.doi.org/10.1074/jbc.M115.665091
↑ Hensbergen PJ, Klychnikov OI, Bakker D, Dragan I, Kelly ML, Minton NP, Corver J, Kuijper EJ, Drijfhout JW, van Leeuwen HC. Clostridium difficile secreted Pro-Pro endopeptidase PPEP-1 (ZMP1/CD2830) modulates adhesion through cleavage of the collagen binding protein CD2831. FEBS Lett. 2015 Dec 21;589(24 Pt B):3952-8. doi: 10.1016/j.febslet.2015.10.027., Epub 2015 Oct 29. PMID:26522134 doi:http://dx.doi.org/10.1016/j.febslet.2015.10.027
↑ Schacherl M, Pichlo C, Neundorf I, Baumann U. Structural Basis of Proline-Proline Peptide Bond Specificity of the Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile. Structure. 2015 Jul 21. pii: S0969-2126(15)00271-3. doi:, 10.1016/j.str.2015.06.018. PMID:26211609 doi:http://dx.doi.org/10.1016/j.str.2015.06.018

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5a0r"

@@ Line 4: / Line 4: @@
 == 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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.251&#8491;</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>

5a0r

From Proteopedia

Current revision

Product peptide-bound structure of metalloprotease Zmp1 variant E143A from Clostridium difficile

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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