InterPro domain: IPR036320

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'.

This N-terminal domain is found in various family 3 glycosyl transferases, including anthranilate phosphoribosyltransferase (TrpD, 2.4.2.18 ) [ 2 ] and thymidine phosphorylase ( 2.4.2.2 ). All these proteins can transfer a phosphorylated ribose substrate. Thymidine phosphorylase catalyses the reversible phosphorolysis of thymidine, deoxyuridine and their analogues to their respective bases and 2-deoxyribose 1-phosphate [ 3 ]. This enzyme regulates the availability of thymidine and is therefore essential to nucleic acid metabolism. It promotes metastasis in Hepatocellular carcinoma (HCC) and may serve as a marker of poor prognosis in HCC, being a potential target for the treatment of HCC [ 4 ]. Thymidine phosphorylase is also involved platelet activation and thrombosis leading to the development of cardiovascular diseases, thus, it has been suggested as a new target for cardiovascular disease treatment [ 4 ].

1. A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem. J. 326 ( Pt 3), 929-39
2. Anthranilate phosphoribosyl transferase (TrpD) generates phosphoribosylamine for thiamine synthesis from enamines and phosphoribosyl pyrophosphate. ACS Chem Biol 8, 242-8
3. Thymidine phosphorylase promotes metastasis and serves as a marker of poor prognosis in hepatocellular carcinoma. Lab Invest 97, 903-912
4. Thymidine phosphorylase: A potential new target for treating cardiovascular disease. Trends Cardiovasc Med 28, 157-171