PDBsum entry 4eeg

Transferase

PDB id: 4eeg

Contents

Protein chain

273 a.a.

Ligands

GAL-NAG ×3

UDP ×3

GOL ×4

SO4 ×10

Metals

_MN ×3

Waters ×517

PDB id:

4eeg

Name:

Transferase

Title:

Crystal structure of human m340h-beta-1,4-galactosyltransferase-1 (m340h-b4gal-t1) in complex with glcnac-beta1,6-gal-beta

Structure:

Beta-1,4-galactosyltransferase 1. Chain: a, b, c. Fragment: catalytic domain. Synonym: beta-1,4-galtase 1, beta4gal-t1, b4gal-t1, udp-gal:beta- glcnac beta-1,4-galactosyltransferase 1, udp-galactose:beta-n- acetylglucosamine beta-1,4-galactosyltransferase 1, lactose synthase a protein, n-acetyllactosamine synthase, nal synthase, beta-n- acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase, beta- n-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: b4galt1, ggtb2. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.20Å R-factor: 0.202 R-free: 0.244

Authors:

B.Ramakrishnan,P.K.Qasba

Key ref:

B.Ramakrishnan et al. (2012). Binding of N-acetylglucosamine (GlcNAc) β1-6-branched oligosaccharide acceptors to β4-galactosyltransferase I reveals a new ligand binding mode. J Biol Chem, 287, 28666-28674. PubMed id: 22740701

Date:

28-Mar-12 Release date: 04-Jul-12

Protein chains

P15291  (B4GT1_HUMAN) -  Beta-1,4-galactosyltransferase 1 from Homo sapiens

Seq: 398 a.a.

Struc: 273 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.4.1.- - ?????
• Enzyme class 2: E.C.2.4.1.22 - lactose synthase.
• Reaction: D-glucose + UDP-alpha-D-galactose = lactose + UDP + H⁺

D-glucose (Bound ligand (Het Group name = GAL) corresponds exactly) + UDP-alpha-D-galactose = lactose + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

• Enzyme class 3: E.C.2.4.1.275 - neolactotriaosylceramide beta-1,4-galactosyltransferase.
• Reaction: a beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)- Cer(d18:1(4E)) + UDP-alpha-D-galactose = a neolactoside nLc4Cer(d18:1(4E)) + UDP + H⁺

beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)- Cer(d18:1(4E)) + UDP-alpha-D-galactose = neolactoside nLc4Cer(d18:1(4E)) + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

• Enzyme class 4: E.C.2.4.1.38 - beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase.
• Reaction: an N-acetyl-beta-D-glucosaminyl derivative + UDP-alpha-D-galactose = a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H⁺

N-acetyl-beta-D-glucosaminyl derivative + UDP-alpha-D-galactose = beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

• Enzyme class 5: E.C.2.4.1.90 - N-acetyllactosamine synthase.
• Reaction: N-acetyl-D-glucosamine + UDP-alpha-D-galactose = beta-D-galactosyl- (1->4)-N-acetyl-D-glucosamine + UDP + H⁺

N-acetyl-D-glucosamine (Bound ligand (Het Group name = NAG) matches with 93.33% similarity) + UDP-alpha-D-galactose = beta-D-galactosyl- (1->4)-N-acetyl-D-glucosamine + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Biol Chem 287:28666-28674 (2012)

PubMed id: 22740701

Binding of N-acetylglucosamine (GlcNAc) β1-6-branched oligosaccharide acceptors to β4-galactosyltransferase I reveals a new ligand binding mode.

B.Ramakrishnan, E.Boeggeman, P.K.Qasba.

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.