title: Structural basis of chitin oligosaccharide deacetylation.
abstract: Cell signaling and other biological activities of chitooligosaccharides (COSs) seem to be dependent not only on the degree of polymerization, but markedly on the specific de-N-acetylation pattern. Chitin de-N-acetylases (CDAs) catalyze the hydrolysis of the acetamido group in GlcNAc residues of chitin, chitosan, and COS. A major challenge is to understand how CDAs specifically define the distribution of GlcNAc and GlcNH2 moieties in the oligomeric chain. We report the crystal structure of the Vibrio cholerae CDA in four relevant states of its catalytic cycle. The two enzyme complexes with chitobiose and chitotriose represent the first 3D structures of a CDA with its natural substrates in a productive mode for catalysis, thereby unraveling an induced-fit mechanism with a significant conformational change of a loop closing the active site. We propose that the deacetylation pattern exhibited by different CDAs is governed by critical loops that shape and differentially block accessible subsites in the binding cleft of CE4 enzymes.
authors.affiliation: Laboratory of Biochemistry, Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona (Spain).
authors.forename: Eduardo
authors.initials: E
authors.lastname: Andrés
authors.forename: David
authors.initials: D
authors.lastname: Albesa-Jové
authors.forename: Xevi
authors.initials: X
authors.lastname: Biarnés
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Moerschbacher
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Guerin
authors.forename: Antoni
authors.initials: A
authors.lastname: Planas
mesh_terms: D000107:Acetylation; D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D055162:Biocatalysis; D020134:Catalytic Domain; D002686:Chitin / Q000737:chemistry; D002688:Chitinases / Q000737:chemistry* / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry; D007700:Kinetics; D062105:Molecular Docking Simulation; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D014312:Trisaccharides / Q000737:chemistry; D014734:Vibrio cholerae / Q000201:enzymology
chemical_list: D004187:Disaccharides; D009844:Oligosaccharides; D014312:Trisaccharides; D002686:Chitin; C041161:chitotriose; C032438:chitobiose; D002688:Chitinases; D000117:Acetylglucosamine
keywords: binding modes; bioorganic chemistry; enzyme catalysis; enzyme-substrate complexes; structure elucidation