5TJN

Crystal structure of GTB + B trisaccharide (native)

Summary for 5TJN

• Entry DOI: 10.2210/pdb5tjn/pdb
• Related: 5TJK 5TJL 5TJM 5TJO 5TJP
• Descriptor: Histo-blood group ABO system transferase, alpha-L-fucopyranose-(1-2)-[alpha-D-galactopyranose-(1-3)]octyl beta-D-galactopyranoside, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: glycosyltransferases, histo blood group enzymes, product trisaccharide, gt-a fold, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 35245.67

Authors

Legg, M.S.G.,Gagnon, S.M.L.,Evans, S.V. (deposition date: 2016-10-04, release date: 2017-06-14, Last modification date: 2023-10-04)

Primary citation

Gagnon, S.M.L.,Legg, M.S.G.,Sindhuwinata, N.,Letts, J.A.,Johal, A.R.,Schuman, B.,Borisova, S.N.,Palcic, M.M.,Peters, T.,Evans, S.V.
High-resolution crystal structures and STD NMR mapping of human ABO(H) blood group glycosyltransferases in complex with trisaccharide reaction products suggest a molecular basis for product release.
Glycobiology, 27:966-977, 2017

PubMed Abstract: The human ABO(H) blood group A- and B-synthesizing glycosyltransferases GTA and GTB have been structurally characterized to high resolution in complex with their respective trisaccharide antigen products. These findings are particularly timely and relevant given the dearth of glycosyltransferase structures collected in complex with their saccharide reaction products. GTA and GTB utilize the same acceptor substrates, oligosaccharides terminating with α-l-Fucp-(1→2)-β-d-Galp-OR (where R is a glycolipid or glycoprotein), but use distinct UDP donor sugars, UDP-N-acetylgalactosamine and UDP-galactose, to generate the blood group A (α-l-Fucp-(1→2)[α-d-GalNAcp-(1→3)]-β-d-Galp-OR) and blood group B (α-l-Fucp-(1→2)[α-d-Galp-(1→3)]-β-d-Galp-OR) determinant structures, respectively. Structures of GTA and GTB in complex with their respective trisaccharide products reveal a conflict between the transferred sugar monosaccharide and the β-phosphate of the UDP donor. Mapping of the binding epitopes by saturation transfer difference NMR measurements yielded data consistent with the X-ray structural results. Taken together these data suggest a mechanism of product release where monosaccharide transfer to the H-antigen acceptor induces active site disorder and ejection of the UDP leaving group prior to trisaccharide egress.

PubMed: 28575295
DOI: 10.1093/glycob/cwx053

Experimental method

X-RAY DIFFRACTION (1.47 Å)