title: Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases.
abstract: The regions surrounding the catalytic amino acids previously identified in a few "retaining" O-glycosyl hydrolases (EC 3.2.1) have been analyzed by hydrophobic cluster analysis and have been used to define sequence motifs. These motifs have been found in more than 150 glycosyl hydrolase sequences representing at least eight established protein families that act on a large variety of substrates. This allows the localization and the precise role of the catalytic residues (nucleophile and acid catalyst) to be predicted for each of these enzymes, including several lysosomal glycosidases. An identical arrangement of the catalytic nucleophile was also found for S-glycosyl hydrolases (myrosinases; EC 3.2.3.1) for which the acid catalyst is lacking. A (beta/alpha)8 barrel structure has been reported for two of the eight families of proteins that have been grouped. It is suggested that the six other families also share this fold at their catalytic domain. These enzymes illustrate how evolutionary events led to a wide diversification of substrate specificity with a similar disposition of identical catalytic residues onto the same ancestral (beta/alpha)8 barrel structure.
authors.affiliation: Centre de Recherches sur les Macromolécules Végétales, Centre National de la Recherche Scientifique, Grenoble, France.
authors.forename: B
authors.initials: B
authors.lastname: Henrissat
authors.forename: I
authors.initials: I
authors.lastname: Callebaut
authors.forename: S
authors.initials: S
authors.lastname: Fabrega
authors.forename: P
authors.initials: P
authors.lastname: Lehn
authors.forename: J P
authors.initials: JP
authors.lastname: Mornon
authors.forename: G
authors.initials: G
authors.lastname: Davies
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D005075:Biological Evolution; D016000:Cluster Analysis; D017124:Conserved Sequence; D016208:Databases, Factual; D006026:Glycoside Hydrolases / Q000145:classification / Q000235:genetics*; D008247:Lysosomes / Q000201:enzymology; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D006026:Glycoside Hydrolases