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 α- and β-bonds. We have observed this trend within groups of glycosidases with completely different folds. We postulate that the evolutionary interconversion between α- and β-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 β anomeric configuration, require a sugar ring distortion, resulting in an axial orientation of the glycosidic bond, equivalent to that of an α glycosidic bond, prior to displacement by nucleophilic substitution.