2A8U

Crystal Structure of Human Galactosyltransferase (GTB) Complexed with Beta-Methyl Lactoside

Summary for 2A8U

• Entry DOI: 10.2210/pdb2a8u/pdb
• Related: 1Z1Z 1ZIP 1ZJ0 1ZJ1 1ZJ2 1ZJ3
• Related PRD ID: PRD_900076
• Descriptor: ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase), beta-D-galactopyranose-(1-4)-methyl beta-D-glucopyranoside, URIDINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: gtb, blood group, abo(h), glycosyltransferase, retaining, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, Golgi stack membrane; Single-pass type II membrane protein: P16442
• Total number of polymer chains: 1
• Total formula weight: 36010.27

Authors

Letts, J.A.,Rose, N.L.,Fang, Y.R.,Barry, C.H.,Borisova, S.N.,Seto, N.O.,Palcic, M.M.,Evans, S.V. (deposition date: 2005-07-09, release date: 2005-12-13, Last modification date: 2023-11-29)

Primary citation

Letts, J.A.,Rose, N.L.,Fang, Y.R.,Barry, C.H.,Borisova, S.N.,Seto, N.O.,Palcic, M.M.,Evans, S.V.
Differential Recognition of the Type I and II H Antigen Acceptors by the Human ABO(H) Blood Group A and B Glycosyltransferases.
J.Biol.Chem., 281:3625-3632, 2006

PubMed Abstract: 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.

PubMed: 16326711
DOI: 10.1074/jbc.M507620200

Experimental method

X-RAY DIFFRACTION (1.69 Å)