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spinqualitylabelsall models 2ah9, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Human M340H-Beta-1,4-Galactosyltransferase-I (M340H-B4Gal-T1) in Complex with Chitotriose

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

beta-1,4-Galactosyltransferase-I (beta4Gal-T1) transfers galactose from, UDP-galactose to N-acetylglucosamine (GlcNAc) residues of the branched, N-linked oligosaccharide chains of glycoproteins. In an N-linked, biantennary oligosaccharide chain, one antenna is attached to the, 3-hydroxyl-(1,3-arm), and the other to the 6-hydroxyl-(1,6-arm) group of, mannose, which is beta-1,4-linked to an N-linked chitobiose, attached to, the aspargine residue of a protein. For a better understanding of the, branch specificity of beta4Gal-T1 towards the GlcNAc residues of, N-glycans, we have carried out kinetic and crystallographic studies with, the wild-type human beta4Gal-T1 (h-beta4Gal-T1) and the mutant, Met340His-beta4Gal-T1 (h-M340H-beta4Gal-T1) in complex with a, GlcNAc-containing pentasaccharide and several GlcNAc-containing, trisaccharides present in N-glycans. The oligosaccharides used were:, pentasaccharide GlcNAcbeta1,2-Manalpha1,6 (GlcNAcbeta1,2-Manalpha1,3)Man;, the 1,6-arm trisaccharide, GlcNAcbeta1,2-Manalpha1,6-Manbeta-OR, (1,2-1,6-arm); the 1,3-arm trisaccharides, GlcNAcbeta1,2-Manalpha1,3-Manbeta-OR (1,2-1,3-arm) and, GlcNAcbeta1,4-Manalpha1,3-Manbeta-OR (1,4-1,3-arm); and the trisaccharide, GlcNAcbeta1,4-GlcNAcbeta1,4-GlcNAc (chitotriose). With the wild-type, h-beta4Gal-T1, the K(m) of 1,2-1,6-arm is approximately tenfold lower than, for 1,2-1,3-arm and 1,4-1,3-arm, and 22-fold lower than for chitotriose., Crystal structures of h-M340H-beta4Gal-T1 in complex with the, pentasaccharide and various trisaccharides at 1.9-2.0A resolution showed, that beta4Gal-T1 is in a closed conformation with the oligosaccharide, bound to the enzyme, and the 1,2-1,6-arm trisaccharide makes the maximum, number of interactions with the enzyme, which is in concurrence with the, lowest K(m) for the trisaccharide. Present studies suggest that, beta4Gal-T1 interacts preferentially with the 1,2-1,6-arm trisaccharide, rather than with the 1,2-1,3-arm or 1,4-1,3-arm of a bi- or tri-antennary, oligosaccharide chain of N-glycan.

Disease

Known diseases associated with this structure: Congenital disorder of glycosylation, type IId OMIM:[137060]

About this Structure

2AH9 is a Single protein structure of sequence from Homo sapiens with CTO, MN, SO4, UDH, DIO, MES and GOL as ligands. Active as N-acetyllactosamine synthase, with EC number 2.4.1.90 Full crystallographic information is available from OCA.

Reference

Oligosaccharide preferences of beta1,4-galactosyltransferase-I: crystal structures of Met340His mutant of human beta1,4-galactosyltransferase-I with a pentasaccharide and trisaccharides of the N-glycan moiety., Ramasamy V, Ramakrishnan B, Boeggeman E, Ratner DM, Seeberger PH, Qasba PK, J Mol Biol. 2005 Oct 14;353(1):53-67. PMID:16157350

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