PDBsum entry 1r81

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protein ligands metals links
Transferase PDB id
Protein chain
266 a.a. *
_HG ×4
Waters ×124
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Glycosyltransferase a in complex with 3-amino-acceptor analo inhibitor and uridine diphosphate-n-acetyl-galactose
Structure: Glycoprotein-fucosylgalactoside alpha-n- acetylgalactosaminyltransferase. Chain: a. Fragment: catalytic domain (residues 63-345). Synonym: glycosyltransferase a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
1.75Å     R-factor:   0.214     R-free:   0.227
Authors: H.P.Nguyen,N.O.L.Seto,Y.Cai,E.K.Leinala,S.N.Borisova,M.M.Pal S.V.Evans
Key ref:
H.P.Nguyen et al. (2003). The influence of an intramolecular hydrogen bond in differential recognition of inhibitory acceptor analogs by human ABO(H) blood group A and B glycosyltransferases. J Biol Chem, 278, 49191-49195. PubMed id: 12972418 DOI: 10.1074/jbc.M308770200
22-Oct-03     Release date:   10-Feb-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P16442  (BGAT_HUMAN) -  Histo-blood group ABO system transferase
354 a.a.
266 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.  - Fucosylgalactoside 3-alpha-galactosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: UDP-alpha-D-galactose + alpha-L-fucosyl-(1->2)-D-galactosyl-R = UDP + alpha-D-galactosyl-(1->3)-(alpha-L-fucosyl-(1->2))-D-galactosyl-R
Bound ligand (Het Group name = AIG)
matches with 57.69% similarity
Bound ligand (Het Group name = UD2)
corresponds exactly
+ alpha-D-galactosyl-(1->3)-(alpha-L-fucosyl-(1->2))-D-galactosyl-R
   Enzyme class 2: E.C.  - Glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: UDP-N-acetyl-alpha-beta-D-galactosamine + glycoprotein-alpha-L-fucosyl- (1->2)-D-galactose = UDP + glycoprotein-N-acetyl-alpha-D-galactosaminyl- (1->3)-(alpha-L-fucosyl-(1->2))-beta-D-galactose
+ glycoprotein-alpha-L-fucosyl- (1->2)-D-galactose
Bound ligand (Het Group name = UD2)
corresponds exactly
+ glycoprotein-N-acetyl-alpha-D-galactosaminyl- (1->3)-(alpha-L-fucosyl-(1->2))-beta-D-galactose
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     transferase activity, transferring hexosyl groups     1 term  


DOI no: 10.1074/jbc.M308770200 J Biol Chem 278:49191-49195 (2003)
PubMed id: 12972418  
The influence of an intramolecular hydrogen bond in differential recognition of inhibitory acceptor analogs by human ABO(H) blood group A and B glycosyltransferases.
H.P.Nguyen, N.O.Seto, Y.Cai, E.K.Leinala, S.N.Borisova, M.M.Palcic, S.V.Evans.
Human ABO(H) blood group glycosyltransferases GTA and GTB catalyze the final monosaccharide addition in the biosynthesis of the human A and B blood group antigens. GTA and GTB utilize a common acceptor, the H antigen disaccharide alpha-l-Fucp-(1-->2)-beta-d-Galp-OR, but different donors, where GTA transfers GalNAc from UDP-GalNAc and GTB transfers Gal from UDP-Gal. GTA and GTB are two of the most homologous enzymes known to transfer different donors and differ in only 4 amino acid residues, but one in particular (Leu/Met-266) has been shown to dominate the selection between donor sugars. The structures of the A and B glycosyltransferases have been determined to high resolution in complex with two inhibitory acceptor analogs alpha-l-Fucp(1-->2)-beta-d-(3-deoxy)-Galp-OR and alpha-l-Fucp-(1-->2)-beta-d-(3-amino)-Galp-OR, in which the 3-hydroxyl moiety of the Gal ring has been replaced by hydrogen or an amino group, respectively. Remarkably, although the 3-deoxy inhibitor occupies the same conformation and position observed for the native H antigen in GTA and GTB, the 3-amino analog is recognized differently by the two enzymes. The 3-amino substitution introduces a novel intramolecular hydrogen bond between O2' on Fuc and N3' on Gal, which alters the minimum-energy conformation of the inhibitor. In the absence of UDP, the 3-amino analog can be accommodated by either GTA or GTB with the l-Fuc residue partially occupying the vacant UDP binding site. However, in the presence of UDP, the analog is forced to abandon the intramolecular hydrogen bond, and the l-Fuc residue is shifted to a less ordered conformation. Further, the residue Leu/Met-266 that was thought important only in distinguishing between donor substrates is observed to interact differently with the 3-amino acceptor analog in GTA and GTB. These observations explain why the 3-deoxy analog acts as a competitive inhibitor of the glycosyltransferase reaction, whereas the 3-amino analog displays complex modes of inhibition.
  Selected figure(s)  
Figure 2.
FIG. 2. Wire-frame models of acceptor analogs co-crystallized with GTA and GTB in the presence and absence of UDP, showing the 2F[o] - F[c] A electron density in red contoured at 0.8 . a, DI (yellow) bound to GTA in the absence of UDP. b, DI (blue) bound to GTB in the absence of UDP. c, AI (white) bound to GTA in the absence of UDP. d, AI (magenta) bound to GTB in the absence of UDP. e, AI (white) bound to GTA in the presence of UDP. f, AI (magenta) bound to GTB in the presence of UDP.
Figure 3.
FIG. 3. Significant contacts observed between GTB and 3-deoxy inhibitor (a) and 3-amino inhibitor (b), both in the absence of UDP. The contacts made by GTA with these two acceptor analogs are similar except for Leu-266, which makes no contact with the 3-amino analog.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 49191-49195) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20154292 N.Sindhuwinata, E.Munoz, F.J.Munoz, M.M.Palcic, H.Peters, and T.Peters (2010).
Binding of an acceptor substrate analog enhances the enzymatic activity of human blood group B galactosyltransferase.
  Glycobiology, 20, 718-723.  
18518825 L.L.Lairson, B.Henrissat, G.J.Davies, and S.G.Withers (2008).
Glycosyltransferases: structures, functions, and mechanisms.
  Annu Rev Biochem, 77, 521-555.  
17850816 A.L.Milac, N.V.Buchete, T.A.Fritz, G.Hummer, and L.A.Tabak (2007).
Substrate-induced conformational changes and dynamics of UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase-2.
  J Mol Biol, 373, 439-451.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.