1zj2
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Crystal Structure of Human Galactosyltransferase (GTB) Complexed with H type I Trisaccharide
OverviewOverview
The human ABO(H) blood group A and B antigens are generated by the, homologous glycosyltransferases A (GTA) and B (GTB), which add the, monosaccharides GalNAc and Gal, respectively, to the cell-surface H, antigens. In the first comprehensive structural study of the recognition, by a glycosyltransferase of a panel of substrates corresponding to, acceptor fragments, 14 high resolution crystal structures of GTA and GTB, have been determined in the presence of oligosaccharides corresponding to, different segments of the type I, (alpha-l-Fucp-(1-->2)-beta-D-Galp-(1-->3)-beta-D-GlcNAcp-OR, where R is a, glycoprotein or glycolipid in natural acceptors) and type II, (alpha-l-Fucp-(1-->2)-beta-D-Galp-(1-->4)-beta-d-GlcNAcp-OR) H antigen, trisaccharides. GTA and GTB differ in only four "critical" amino acid, residues (Arg/Gly-176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268). As, these enzymes both utilize the H antigen acceptors, the four critical, residues had been thought to be involved strictly in donor recognition;, however, we now report that acceptor binding and subsequent transfer are, significantly influenced by two of these residues: Gly/Ser-235 and, Leu/Met-266. Furthermore, these structures show that acceptor recognition, is dominated by the central Gal residue despite the fact that the L-Fuc, residue is required for efficient catalysis and give direct insight into, the design of model inhibitors for GTA and GTB.
DiseaseDisease
Known disease associated with this structure: Blood group, ABO system OMIM:[110300]
About this StructureAbout this Structure
1ZJ2 is a Single protein structure of sequence from Homo sapiens with HG, CL, MN, UDP and DR3 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Differential recognition of the type I and II H antigen acceptors by the human ABO(H) blood group A and B glycosyltransferases., Letts JA, Rose NL, Fang YR, Barry CH, Borisova SN, Seto NO, Palcic MM, Evans SV, J Biol Chem. 2006 Feb 10;281(6):3625-32. Epub 2005 Dec 2. PMID:16326711
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