InterPro domain: IPR005027

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([intenz:2.4.1.-]) and related proteins into distinct sequence based families has been described [ 1 ]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

Glycosyltransferase family 43 GT43 comprises enzymes with only one known activity: beta-glucuronyltransferase(GlcAT-I; 2.4.1.135 ) [ 2 ].

GlcAT-I is a key enzyme involved in the initial steps of proteoglycan synthesis [ 3 ]. GlcAT-I catalyzes the transfer of a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region of trisaccharide Gal-beta-(1-3)-Gal-beta-(1-4)-Xyl of proteoglycans. The enzyme has two subdomains that bind the donor and acceptor substrate separately [ 4 ]. The active site is located at the cleft between both subdomains in which the trisaccharide molecule is oriented perpendicular to the UDP [ 5 ].

1. A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem. J. 326 ( Pt 3), 929-39
2. Cloning and expression of a novel galactoside beta1, 3-glucuronyltransferase involved in the biosynthesis of HNK-1 epitope. J. Biol. Chem. 274, 17115-22
3. Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. FEBS Lett. 459, 415-20
4. Conserved domains of glycosyltransferases. Glycobiology 9, 961-78
5. Structure/function studies of glycosyltransferases. Curr. Opin. Struct. Biol. 9, 563-71