Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lammerts van Bueren A, Fayers-Kerr J, Luo B, Zhang Y, Sollogoub M, Bleriot Y, Rovira C, Davies GJ. Analysis of the Reaction Coordinate of alpha-l-Fucosidases: A Combined Structural and Quantum Mechanical Approach. J Am Chem Soc. 2010 Jan 21. PMID:20092273 doi:10.1021/ja908908q
