Molecular basis of substrate specificity in family 1 glycoside hydrolases.
ss-glycosidases are active upon a large range of substrates. Besides this, subtle changes in the substrate structure may result in large modifications on the ss-glycosidase activity. The characterization of the molecular basis of ss-glycosidases substrate preference may contribute to the comprehension of the enzymatic specificity, a fundamental property of biological systems. ss-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 ss-glycosidase activity. The active site residues forming these interactions and the pattern of the hydrogen bond network are conserved among all ss-glycosidases. The region of the ss-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 ss-glycosidases. Hydrophobic interactions and hydrogen bonds are formed with the aglycone, but the manner in which they control the ss-glycosidase specificity still remains to be determined.
Marana
Sandro R
SR
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brasil. srmarana@iq.usp.br
D000595:Amino Acid Sequence; D001665:Binding Sites; D002236:Carbohydrate Conformation; D006026:Glycoside Hydrolases / Q000145:classification / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016415:Sequence Alignment; D013379:Substrate Specificity
D006027:Glycosides; D006026:Glycoside Hydrolases