Computational analysis of glycoside hydrolase family 1 specificities

Glycoside hydrolase family 1 consists of β‐glucosidases, β‐galactosidases, 6‐phospho‐β‐galactosidases, myrosinases, and other enzymes having similar primary and tertiary structures but diverse specificities. Among these enzymes, β‐glucosidases hydrolyze cellobiose to glucose, and therefore they are key players in any cellulose to glucose process. All family members attack β‐glycosidic bonds between a pyranosyl glycon and an aglycon, but most have little specificity for the aglycon or for the bond configuration. Furthermore, glycon specificity is not absolute. Sixteen family members (six β‐glucosidases, two cyanogenic β‐glucosidases, one 6‐phospho‐β‐galactosidase, two myrosinases, and five β‐glycosidases) have known tertiary structures. We have used automated docking to computationally bind disaccharides with allopyranosyl, galactopyranosyl, glucopyranosyl, mannopyranosyl, 6‐phosphogalactopyranosyl, and 6‐phosphoglucopyranosyl glycons, all linked by β‐(1,2), β‐(1,3), β‐(1,4), and β‐(1,6)‐glycosidic bonds to β‐glucopyranoside aglycons, along with β‐(1,1‐thio)‐allopyranosyl, ‐galactopyranosyl, ‐glucopyranosyl, and ‐mannopyranosyl) β‐glucopyranosides, into all of these structures to investigate the structural determinants of their enzyme specificities. The following are the eight active‐site residues: Glu191, Thr194, Phe205, Asn285, Arg336, Asn376, Trp378, and Trp465 (Zea mays β‐glucosidase numbering), that control a significant amount of glycon specificity. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 1021–1031, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com