PDBsum entry 4fqw

Transferase

PDB id: 4fqw

Contents

Protein chain

271 a.a.

Ligands

UDP

GAL

PG4

Waters ×125

PDB id:

4fqw

Name:

Transferase

Title:

Crystal structure of aaaa+udp+gal at ph 5.0 with mpd as the cryoprotectant

Structure:

Histo-blood group abo system transferase. Chain: a. Synonym: fucosylglycoprotein 3-alpha-galactosyltransferase, fucosylglycoprotein alpha-n-acetylgalactosaminyltransferase, glycoprotein-fucosylgalactoside alpha-n- acetylgalactosaminyltransferase, glycoprotein-fucosylgalactoside alpha-galactosyltransferase, histo-blood group a transferase, a transferase, histo-blood group b transferase, b transferase, nagat, fucosylglycoprotein alpha-n-acetylgalactosaminyltransferase soluble

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: abo. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.02Å R-factor: 0.195 R-free: 0.258

Authors:

A.R.Johal,J.A.Alfaro,R.J.Blackler,B.Schuman,S.N.Borisova,S.V.Evans

Key ref:

A.R.Johal et al. (2014). pH-induced conformational changes in human ABO(H) blood group glycosyltransferases confirm the importance of electrostatic interactions in the formation of the semi-closed state. Glycobiology, 24, 237-246. PubMed id: 24265507 DOI: 10.1093/glycob/cwt098

Date:

25-Jun-12 Release date: 25-Dec-13

Protein chain

P16442  (BGAT_HUMAN) -  Histo-blood group ABO system transferase from Homo sapiens

Seq: 354 a.a.

Struc: 271 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.4.1.37 - fucosylgalactoside 3-alpha-galactosyltransferase.
• Reaction: an alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-alpha-D- galactose = an alpha-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->2)]-beta-D- galactosyl derivative + UDP + H⁺

alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-alpha-D- galactose = alpha-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->2)]-beta-D- galactosyl derivative + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

• Enzyme class 2: E.C.2.4.1.40 - glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase.
• Reaction: an alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-N-acetyl- alpha-D-galactosamine = an N-acetyl-alpha-D-galactosaminyl-(1->3)-[alpha- L-fucosyl-(1->2)]-beta-D-galactosyl derivative + UDP + H⁺

alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-N-acetyl- alpha-D-galactosamine = N-acetyl-alpha-D-galactosaminyl-(1->3)-[alpha- L-fucosyl-(1->2)]-beta-D-galactosyl derivative + 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

Added reference

DOI no: 10.1093/glycob/cwt098

Glycobiology 24:237-246 (2014)

PubMed id: 24265507

pH-induced conformational changes in human ABO(H) blood group glycosyltransferases confirm the importance of electrostatic interactions in the formation of the semi-closed state.

A.R.Johal, R.J.Blackler, J.A.Alfaro, B.Schuman, S.Borisova, S.V.Evans.

ABSTRACT

The homologous human ABO(H) A and B blood group glycosyltransferases GTA and GTB have two mobile polypeptide loops surrounding their active sites that serve to allow substrate access and product egress and to recognize and sequester substrates for catalysis. Previous studies have established that these enzymes can move from the "open" state to the "semi-closed" then "closed" states in response to addition of a substrate. The contribution of electrostatic interactions to these conformational changes has now been demonstrated by the determination at various pH of the structures of GTA, GTB and the chimeric enzyme ABBA. At near-neutral pH, GTA displays the closed state in which both mobile loops order around the active site, whereas ABBA and GTB display the open state. At low pH, the apparent protonation of the DXD motif in GTA leads to the expulsion of the donor analog to yield the open state, whereas at high pH, both ABBA and GTB form the semi-closed state in which the first mobile loop becomes an ordered α-helix. Step-wise deprotonation of GTB in increments of 0.5 between pH 6.5 and 10.0 shows that helix ordering is gradual, which indicates that the formation of the semi-closed state is dependent on electrostatic forces consistent with the binding of substrate. Spectropolarimetric studies of the corresponding stand-alone peptide in solution reveal no tendency toward helix formation from pH 7.0 to 10.0, which shows that pH-dependent stability is a product of the larger protein environment and underlines the importance of substrate in active site ordering.