4EEG

Crystal structure of human M340H-beta-1,4-galactosyltransferase-1 (M340H-B4GAL-T1) in complex with GLCNAC-BETA1,6-Gal-Beta

Summary for 4EEG

• Entry DOI: 10.2210/pdb4eeg/pdb
• Related: 4EE3 4EE4 4EE5 4EEA 4EEM 4EEO
• Descriptor: Beta-1,4-galactosyltransferase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-6)-beta-D-galactopyranose, URIDINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: gt-a fold, glycosyltransferase, udp-galactose, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 102176.04

Authors

Ramakrishnan, B.,Qasba, P.K. (deposition date: 2012-03-28, release date: 2012-07-04, Last modification date: 2024-11-20)

Primary citation

Ramakrishnan, B.,Boeggeman, E.,Qasba, P.K.
Binding of N-acetylglucosamine (GlcNAc) beta 1-6-branched oligosaccharide acceptors to beta 4-galactosyltransferase I reveals a new ligand binding mode.
J.Biol.Chem., 287:28666-28674, 2012

PubMed Abstract: N-acetyllactosamine is the most prevalent disaccharide moiety in the glycans on the surface of mammalian cells and often found as repeat units in the linear and branched polylactosamines, known as i- and I-antigen, respectively. The β1-4-galactosyltransferase-I (β4Gal-T1) enzyme is responsible for the synthesis of the N-acetyllactosamine moiety. To understand its oligosaccharide acceptor specificity, we have previously investigated the binding of tri- and pentasaccharides of N-glycan with a GlcNAc at their nonreducing end and found that the extended sugar moiety in these acceptor substrates binds to the crevice present at the acceptor substrate binding site of the β4Gal-T1 molecule. Here we report seven crystal structures of β4Gal-T1 in complex with an oligosaccharide acceptor with a nonreducing end GlcNAc that has a β1-6-glycosidic link and that are analogous to either N-glycan or i/I-antigen. In the crystal structure of the complex of β4Gal-T1 with I-antigen analog pentasaccharide, the β1-6-branched GlcNAc moiety is bound to the sugar acceptor binding site of the β4Gal-T1 molecule in a way similar to the crystal structures described previously; however, the extended linear tetrasaccharide moiety does not interact with the previously found extended sugar binding site on the β4Gal-T1 molecule. Instead, it interacts with the different hydrophobic surface of the protein molecule formed by the residues Tyr-276, Trp-310, and Phe-356. Results from the present and previous studies suggest that β4Gal-T1 molecule has two different oligosaccharide binding regions for the binding of the extended oligosaccharide moiety of the acceptor substrate.

PubMed: 22740701
DOI: 10.1074/jbc.M112.373514

Experimental method

X-RAY DIFFRACTION (2.2 Å)