Molecular basis of substrate specificity in family 1 glycoside hydrolases

Abstract

β-glycosidases are active upon a large range of substrates. Besides this, subtle changes in the substrate structure may result in large modifications on the β-glycosidase activity. The characterization of the molecular basis of β-glycosidases substrate preference may contribute to the comprehension of the enzymatic specificity, a fundamental property of biological systems. β-glycosidases specificity for the monosaccharide of the substrate nonreducing end (glycone) is controlled by a hydrogen bond network involving at least 5 active site amino acid residues and 4 substrate hydroxyls. From these residues, a glutamate, which interacts with hydroxyls 4 and 6, seems to be a key element in the determination of the preference for fucosides, glucosides and galactosides. Apart from this, interactions with the hydroxyl 2 are essential to the β-glycosidase activity. The active site residues forming these interactions and the pattern of the hydrogen bond network are conserved among all β-glycosidases. The region of the β-glycosidase active site that interacts with the moiety (called aglycone) which is bound to the glycone is formed by several subsites (1 to 3). However, the majority of the non-covalent interactions with the aglycone is concentrated in the first one, which presents a variable spatial structure and amino acid composition. This structural variability is in accordance with the high diversity of aglycones recognized by β-glycosidases. Hydrophobic interactions and hydrogen bonds are formed with the aglycone, but the manner in which they control the β-glycosidase specificity still remains to be determined. © 2006 IUBMB.