7cfl | pdb_00007cfl
X-ray structure of autolysin Acd24020 catalytic domain from Clostridium difficile
Structural highlights
FunctionPublication Abstract from PubMedAutolysin is a lytic enzyme that hydrolyzes peptidoglycans of the bacterial cell wall, with a catalytic domain and cell wall-binding (CWB) domains, to be involved in different physiological functions that require bacterial cell wall remodeling. We identified a novel autolysin, Acd24020, from Clostridioides (Clostridium) difficile (C. difficile), with an endopeptidase catalytic domain belonging to the NlpC/P60 family and three bacterial Src-homology 3 domains as CWB domains. The catalytic domain of Acd24020 (Acd24020-CD) exhibited C. difficile-specific lytic activity equivalent to Acd24020, indicating that Acd24020-CD has full-function as a lytic enzyme by itself. To elucidate the specific peptidoglycan-recognition and catalytic reaction mechanisms of Acd24020-CD, biochemical characterization, X-ray structure determination, a modeling study of the enzyme/substrate complex, and mutagenesis analysis were performed. Acd24020-CD has an hourglass-shaped substrate-binding groove across the molecule, which is responsible for recognizing the direct 3-4 cross-linking structure unique to C. difficile peptidoglycan. Based on the X-ray structure and modeling study, we propose a dynamic Cys/His catalyzing mechanism, in which the catalytic Cys299 and His354 residues dynamically change their conformations to complement each step of the enzyme catalytic reaction. Structural and biochemical characterizations of the novel autolysin Acd24020 from Clostridioides difficile and its full-function catalytic domain as a lytic enzyme.,Sekiya H, Tamai E, Kawasaki J, Murakami K, Kamitori S Mol Microbiol. 2020 Nov 2. doi: 10.1111/mmi.14636. PMID:33140473[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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