5a0x

Substrate peptide-bound structure of metalloprotease Zmp1 variant E143AY178F from Clostridium difficile

spinqualitylabelsall models 5a0x, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5a0x is a 4 chain structure with sequence from Clostridioides difficile 630. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN NonStd Res: ACE, NH2 Related: 5a0p, 5a0r, 5a0s Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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