title: Structure of bovine alpha-1,3-galactosyltransferase and its complexes with UDP and DPGal inferred from molecular modeling.
abstract: A homology model of alpha-1,3-galactosyltransferase (alpha-1,3-GalT), the retaining enzyme responsible for the formation of alpha-galactosyl epitopes, has been developed by means of molecular modeling using the SpsA glycosyltransferase structure. A protein-ligand docking approach was used to model alpha-1,3-GalT complexed with UDP and UDP-Gal. The comparison of structural features found in the alpha-1,3-GalT homology model with available structural data on this class of enzymes revealed similarities in the UDP-binding pocket. In the predicted structure of the complexes, the pyrophosphate interacts with the DVD motif (Asp-225, Val-226, and Asp-227) of alpha-1,3-GalT through the Mn(2+) cation. The uridine part of the UDP binds into the well-defined cavity that consists of Phe-134, Tyr-139, Ile-140, Val-136, Arg-194, Arg-202, Lys-209, Asp-173, His-218, and Thr-137 in a conformation that is generally observed in the crystal structures of other glycosyltransferase complexes.
authors.affiliation: GlycoDesign Inc., Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Rao
authors.forename: I
authors.initials: I
authors.lastname: Tvaroska
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014530:Uridine Diphosphate / Q000737:chemistry* / Q000378:metabolism*; D014531:Uridine Diphosphate Galactose / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D014531:Uridine Diphosphate Galactose; D014530:Uridine Diphosphate; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase