2wvt

Crystal structure of an alpha-L-fucosidase GH29 from Bacteroides thetaiotaomicron in complex with a novel iminosugar fucosidase inhibitor

spinqualitylabelsall models 2wvt, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wvt is a 2 chain structure with sequence from Bacteroides thetaiotaomicron VPI-5482. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: FHN, GOL, IMD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8A3I4_BACTN Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The enzymatic hydrolysis of alpha-l-fucosides is of importance in cancer, bacterial infections, and fucosidosis, a neurodegenerative lysosomal storage disorder. Here we show a series of snapshots along the reaction coordinate of a glycoside hydrolase family GH29 alpha-l-fucosidase unveiling a Michaelis (ES) complex in a (1)C(4) (chair) conformation and a covalent glycosyl-enzyme intermediate in (3)S(1) (skew-boat). First principles metadynamics simulations on isolated alpha-l-fucose strongly support a (1)C(4)<-->(3)H(4)<-->(3)S(1) conformational itinerary for the glycosylation step of the reaction mechanism and indicate a strong "preactivation" of the (1)C(4) complex to nucleophilic attack as reflected by free energy, C1-O1/O5-C1 bond length elongation/reduction, C1-O1 bond orientation, and positive charge development around the anomeric carbon. Analysis of an imino sugar inhibitor is consistent with tight binding of a chair-conformed charged species. Analysis of the Reaction Coordinate of alpha-l-Fucosidases: A Combined Structural and Quantum Mechanical Approach.,Lammerts van Bueren A, Fayers-Kerr J, Luo B, Zhang Y, Sollogoub M, Bleriot Y, Rovira C, Davies GJ J Am Chem Soc. 2010 Jan 21. PMID:20092273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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