title: Evolutionary and mechanistic relationships between glycosidases acting on alpha- and beta-bonds.
abstract: Because of the fast accumulation of sequences derived from genome sequencing efforts, the sampling of the sequence space in glycosidase and related enzyme families is such that sensitive sequence similarity detection methods like PSI-BLAST are now able to reveal distant, but clear, structural and evolutionary relations between glycosidases acting on alpha- and beta-bonds. We have observed this trend within groups of glycosidases with completely different folds. We postulate that the evolutionary interconversion between alpha- and beta-acting glycosidases was greatly facilitated by the fact that both types share a similar axial orientation of the glycosidic bond in the reactive bound substrate. Glycosides in the beta anomeric configuration, require a sugar ring distortion, resulting in an axial orientation of the glycosidic bond, equivalent to that of an alpha glycosidic bond, prior to displacement by nucleophilic substitution.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, UMR6098, Centre National de la Recherche Scientifique, Universités d'Aix-Marseille I & II, Case 932, 163 Avenue de Luminy, 13288 Marseille cedex 9, France.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Stam
authors.forename: Eric
authors.initials: E
authors.lastname: Blanc
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Coutinho
authors.forename: Bernard
authors.initials: B
authors.lastname: Henrissat
mesh_terms: D019143:Evolution, Molecular; D006026:Glycoside Hydrolases / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D006026:Glycoside Hydrolases