Structural, functional, and mutagenesis studies of UDP-glycosyltransferases.

The biosynthesis of the complex carbohydrates that govern many cellular functions requires the action of a diverse range of selective glycosyltransferases (GTs). Uridine diphosphate sugar-utilizing GTs (UGTs) account for the majority of characterized GTs. GTs have been classified into families (currently 92) based on amino-acid sequence similarity. However, as amino-acid sequence similarity cannot reliable predict catalytic mechanism, GTs have also been grouped into four clans based on catalytic mechanism and structural fold. GTs catalyze glycosidic bond formation with two possible stereochemical outcomes: inversion or retention of anomeric configuration. All UGTs also belong to one of two distinct structural folds, GT-A and GT-B. UGTs have conserved residues that are associated with nucleotide diphosphate sugar recognition and acceptor recognition. UGT diversification has been performed using in vitro DNA recombination, domain swapping, and random mutagenesis.