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

Citation:
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 beta1-4-galactosyltransferase-I (beta4Gal-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 beta4Gal-T1 molecule. Here we report seven crystal structures of beta4Gal-T1 in complex with an oligosaccharide acceptor with a nonreducing end GlcNAc that has a beta1-6-glycosidic link and that are analogous to either N-glycan or i/I-antigen. In the crystal structure of the complex of beta4Gal-T1 with I-antigen analog pentasaccharide, the beta1-6-branched GlcNAc moiety is bound to the sugar acceptor binding site of the beta4Gal-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 beta4Gal-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 beta4Gal-T1 molecule has two different oligosaccharide binding regions for the binding of the extended oligosaccharide moiety of the acceptor substrate.
PDB ID: 4EEGDownload
MMDB ID: 101056
PDB Deposition Date: 2012/3/28
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4EEG: monomeric; determined by author
Molecular Components in 4EEG
Label Count Molecule
Protein (1 molecule)
1
Beta-1,4-galactosyltransferase 1(Gene symbol: B4GALT1)
Molecule annotation
Chemicals (8 molecules)
1
1
2
1
3
1
4
1
5
1
6
3
* Click molecule labels to explore molecular sequence information.

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