Evolutionary and mechanistic relationships between glycosidases acting on alpha- and beta-bonds.
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.
Stam
Mark R
MR
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.
Blanc
Eric
E
Coutinho
Pedro M
PM
Henrissat
Bernard
B
D019143:Evolution, Molecular; D006026:Glycoside Hydrolases / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
D006026:Glycoside Hydrolases