9ubf | pdb_00009ubf

X-ray structure of Clostridioides difficile autolysin Acd33800 catalytic domain

spinqualitylabelsall models 9ubf, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ubf is a 2 chain structure with sequence from Clostridioides difficile. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.45Å Ligands: MHO, OCS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q180M8_CLOD6 Publication Abstract from PubMed Clostridioides difficile is a major pathogen of pseudomembranous colitis, and new antimicrobial agents are needed for its treatment. Autolysins are peptidoglycan-degrading enzymes that generally reorganize the cell wall during cell division but kill bacteria by bacteriolysis when applied from outside the bacterial cell. Therefore, they have potential as novel therapeutic agents for the treatment of infectious diseases. We surveyed the genome of C. difficile strain 630 and identified two virtually identical autolysin genes, cdCwlT33800 and cdCwlT, with a lysozyme-like domain and endopeptidase domain. The entire region and each domain of the two proteins were expressed, purified, and assayed for bacteriolytic activity. Only the individual endopeptidase domain variants exhibited bacteriolytic activity against C. difficile. We also investigated the optimal pH and salt concentration, the effects of metal ions, thermostability, long-term storage, and the species specificity of the CdCwlT33800 endopeptidase domain (CdCwlT33800CD2). The structure of CdCwlT33800CD2 was elucidated by X-ray crystallography at a resolution of 1.45 A. The overall structure was spherical and consisted of five helices and eight beta-strands, with a 28 A substrate-binding groove, at the center of which the catalytic residues of Cys242 and His296 were located. The structure of the substrate-enzyme complex was proposed through modeling and mutagenic analyses of CdCwlT33800CD2.IMPORTANCEClostridioides difficile is a bacterium that causes severe colitis and life-threatening diarrhea, particularly after antibiotic treatment. Since current therapies are not always effective and resistance to drugs continues to increase, there is an urgent need for new treatment strategies. One promising approach is the use of lytic enzymes, which break down the bacterial cell wall and lead to bacterial death. These enzymes include autolysins, which are produced by bacteria themselves and phage-derived endolysins. In the present study, we identified a novel autolysin from C. difficile and analyzed its biochemical characteristics and structure. The present results provide insights into the development of enzyme-based therapies to combat C. difficile infections and may lead to effective alternatives to conventional antibiotics. Biochemical characterization and X-ray structural and mutagenic analyses of the putative autolysin CdCwlT33800 catalytic domain from Clostridioides difficile.,Sekiya H, Nonaka Y, Kamitori S, Tamai E Appl Environ Microbiol. 2025 Sep 16:e0121625. doi: 10.1128/aem.01216-25. PMID:40956107 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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