There are approximately 100 known members of the family 3 group of glycosid
e hydrolases, most of which are classified as beta-glucosidases and origina
te from microorganisms. The only family 3 glycoside hydrolase for which a t
hree-dimensional structure is available is a beta-glucan exohydrolase from
barley. The structural coordinates of the barley enzyme is used here to mod
el representatives from distinct phylogenetic clusters within the family. T
he majority of family 3 hydrolases have an NH2-terminal (alpha/beta)(8) bar
rel connected by a short linker to a second domain, which adopts an (alpha/
beta), sandwich fold. In two bacterial beta-glucosidases, the order of the
domains is reversed. The catalytic nucleophile, equivalent to D285 of the b
arley beta-glucan exohydrolase, is absolutely conserved across the family.
It is located on domain 1, in a shallow site pocket near the interface of t
he domains. The likely catalytic acid in the barley enzyme, E491, is on dom
ain 2. Although similarly positioned acidic residues are present in closely
related members of the family, the equivalent amino acid in more distantly
related members is either too far from the active site or absent. In the l
atter cases, the role of catalytic acid is probably assumed by other acidic
amino acids from domain 1. Proteins 2000;41:257-269. (C) 2000 Wiley-Liss,
Inc.