5A0X

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

Summary for 5A0X

• Entry DOI: 10.2210/pdb5a0x/pdb
• Related: 5A0P 5A0R 5A0S
• Descriptor: ZINC METALLOPROTEASE ZMP1, SUBSTRATE PEPTIDE, ZINC ION, ... (4 entities in total)
• Functional Keywords: hydrolase, metalloprotease, proline specificity
• Biological source: CLOSTRIDIUM DIFFICILE; More
• Total number of polymer chains: 4
• Total formula weight: 45499.88

Authors

Schacherl, M.,Pichlo, C.,Neundorf, I.,Baumann, U. (deposition date: 2015-04-23, release date: 2015-08-05, Last modification date: 2024-11-20)

Primary citation

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, 23:1632-, 2015

PubMed Abstract: 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.

PubMed: 26211609
DOI: 10.1016/J.STR.2015.06.018

Experimental method

X-RAY DIFFRACTION (1.7 Å)