Fold recognition study of alpha 3-galactosyltransferase and molecular modeling of the nucleotide sugar-binding domain

The structure and fold of the enzyme responsible for the biosynthesis of th e xenotransplantation antigen, namely pig alpha 3 galactosyltransferase, ha s been studied by means of computational methods. Secondary structure predi ctions indicated that alpha 3-galactosyltransferase and related protein fam ily members, including blood group A and B transferases and Forssman syntha se, are likely to consist of alternating alpha-helices and beta-strands, Fo ld recognition studies predicted that alpha 3-galactosyltransferase shares the same fold as the T4 phage DNA-modifying enzyme beta-glucosyltransferase . This latter enzyme displays a strong structural resemblance with the core of glycogen phosphorylase b. By using the three-dimensional structure of b eta-glucosyltransferase and of several glycogen phosphorylases, the nucleot ide binding domain of pig alpha 3-galactosyltransferase was built by knowle dge-based methods. Both the UDP-galactose ligand and a divalent cation were included in the model during the refinement procedure. The final three-dim ensional model is in agreement with our present knowledge of the biochemist ry and mechanism of alpha 3-galactosyltransferases.