PDBsum entry 3v0q

Transferase

PDB id: 3v0q

Contents

Protein chains

297 a.a.

Ligands

UDP ×2

BHE ×2

GOL ×3

SO4 ×2

Metals

_MN ×2

Waters ×636

PDB id:

3v0q

Name:

Transferase

Title:

Crystal structure of the fucosylgalactoside alpha n- acetylgalactosaminyltransferase (gta, cisab mutant l266g, g268a) in complex with udp and h-antigen acceptor

Structure:

Histo-blood group abo system transferase. Chain: a, b. Fragment: extracellular catalytic domain. 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,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ab0, abo. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.80Å R-factor: 0.152 R-free: 0.191

Authors:

M.M.Palcic,R.Jorgensen

Key ref:

R.Jørgensen et al. (2013). Base-modified donor analogues reveal novel dynamic features of a glycosyltransferase. J Biol Chem, 288, 26201-26208. PubMed id: 23836908 DOI: 10.1074/jbc.M113.465963

Date:

08-Dec-11 Release date: 23-Jan-13

Protein chains

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

Seq: 354 a.a.

Struc: 297 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

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: 10.1074/jbc.M113.465963

J Biol Chem 288:26201-26208 (2013)

PubMed id: 23836908

Base-modified donor analogues reveal novel dynamic features of a glycosyltransferase.

R.Jørgensen, T.Pesnot, H.J.Lee, M.M.Palcic, G.K.Wagner.

ABSTRACT

Glycosyltransferases (GTs) are enzymes that are involved, as Nature's "glycosylation reagents," in many fundamental biological processes including cell adhesion and blood group biosynthesis. Although of similar importance to that of other large enzyme families such as protein kinases and proteases, the undisputed potential of GTs for chemical biology and drug discovery has remained largely unrealized to date. This is due, at least in part, to a relative lack of GT inhibitors and tool compounds for structural, mechanistic, and cellular studies. In this study, we have used a novel class of GT donor analogues to obtain new structural and enzymological information for a representative blood group GT. These analogues interfere with the folding of an internal loop and the C terminus, which are essential for catalysis. Our experiments have led to the discovery of an entirely new active site folding mode for this enzyme family, which can be targeted in inhibitor development, similar to the DFG motif in protein kinases. Taken together, our results provide new insights into substrate binding, dynamics, and utilization in this important enzyme family, which can very likely be harnessed for the rational development of new GT inhibitors and probes.