spacer
spacer

PDBsum entry 1g8o

Go to PDB code: 
protein ligands metals links
Transferase PDB id
1g8o
Jmol
Contents
Protein chain
287 a.a. *
Ligands
U5P
Metals
_MN
Waters ×130
* Residue conservation analysis
PDB id:
1g8o
Name: Transferase
Title: Crystallographic structure of the native bovine alpha-1,3- galactosyltransferase catalytic domain
Structure: N-acetyllactosaminide alpha-1,3- galactosyltransferase. Chain: a. Fragment: catalytic domain. Synonym: 13galt, alpha-1,3-galactosyltransferase. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: ggta1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.274     R-free:   0.335
Authors: L.N.Gastinel,C.Bigon,A.K.Misra,O.Hindsgaul,J.H.Shaper, D.H.Joziasse
Key ref:
L.N.Gastinel et al. (2001). Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases. EMBO J, 20, 638-649. PubMed id: 11179209 DOI: 10.1093/emboj/20.4.638
Date:
20-Nov-00     Release date:   20-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P14769  (GGTA1_BOVIN) -  N-acetyllactosaminide alpha-1,3-galactosyltransferase
Seq:
Struc:
368 a.a.
287 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.1.87  - N-acetyllactosaminide 3-alpha-galactosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: UDP-alpha-D-galactose + beta-D-galactosyl-(1->4)-beta-N-acetyl-D- glucosaminyl-R = UDP + alpha-D-galactosyl-(1->3)-beta-D-galactosyl- (1->4)-beta-N-acetylglucosaminyl-R
UDP-alpha-D-galactose
+ beta-D-galactosyl-(1->4)-beta-N-acetyl-D- glucosaminyl-R
=
UDP
Bound ligand (Het Group name = U5P)
matches with 84.00% similarity
+ alpha-D-galactosyl-(1->3)-beta-D-galactosyl- (1->4)-beta-N-acetylglucosaminyl-R
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  

 

 
    Added reference    
 
 
DOI no: 10.1093/emboj/20.4.638 EMBO J 20:638-649 (2001)
PubMed id: 11179209  
 
 
Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases.
L.N.Gastinel, C.Bignon, A.K.Misra, O.Hindsgaul, J.H.Shaper, D.H.Joziasse.
 
  ABSTRACT  
 
alpha1,3-galactosyltransferase (alpha3GalT, EC 2.4.1.151) is a Golgi-resident, type II transmembrane protein that transfers galactose from UDP-alpha-galactose to the terminal N:-acetyllactosamine unit of glycoconjugate glycans, producing the Galalpha1,3Galbeta1,4GlcNAc oligosaccharide structure present in most mammalian glycoproteins. Unlike most other mammals, humans and Old World primates do not possess alpha3GalT activity, which is relevant for the hyperacute rejection observed in pig-to-human xenotransplantation. The crystal structure of the catalytic domain of substrate-free bovine alpha3GalT, solved and refined to 2.3 A resolution, has a globular shape with an alpha/beta fold containing a narrow cleft on one face, and shares a UDP-binding domain (UBD) with the recently solved inverting glycosyltransferases. The substrate-bound complex, solved and refined to 2.5 A, allows the description of residues interacting directly with UDP-galactose. These structural data suggest that the strictly conserved residue E317 is likely to be the catalytic nucleophile involved in galactose transfer with retention of anomeric configuration as accomplished by this enzyme. Moreover, the alpha3GalT structure helps to identify amino acid residues that determine the specificities of the highly homologous ABO histo-blood group and glycosphingolipid glycosyltransferases.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Close-up stereoview of the 3GalT UDP-Gal-binding site. (A) Hg-UDP-Gal is shown in ball-and-stick form and color coded depending on the nature of the atoms; the Mn2+ ion is shown as a pink sphere. Amino acid side chains interacting with Hg-UDP-Gal are shown in ball-and-stick form in yellow. The acidic residues from the motifs D225VD227 and the D316E317 are shown in ball-and-stick form in red. The four amino acid side chains of 3GalT residues at positions equivalent to the residues distinguishing human A-GT from B-GT are shown in ball-and-stick form in blue. (B) Stereoview of the electron density map (2F[o] - F[c], 1 ) of the Hg-UDP-Gal-binding site.
Figure 6.
Figure 6 Schematic representation of the 3GalT-retaining reaction mechanism. Steps (A) and (B) are derived from the substrate-bound 3GalT structure. The acceptor substrate schematized in steps (C) and (D) is a lactosamine-type glycan (Gal 1,4GlcNAc-R).
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 638-649) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20042032 F.Yamamoto, M.Yamamoto, and A.Blancher (2010).
Generation of histo-blood group B transferase by replacing the N-acetyl-d-galactosamine recognition domain of human A transferase with the galactose-recognition domain of evolutionarily related murine alpha1,3-galactosyltransferase.
  Transfusion, 50, 622-630.  
20820649 G.L.Zhang, L.H.Zhang, and X.S.Ye (2010).
Concise syntheses of selective inhibitors against α-1,3-galactosyltransferase.
  Org Biomol Chem, 8, 5062-5068.  
20030628 R.Hurtado-Guerrero, T.Zusman, S.Pathak, A.F.Ibrahim, S.Shepherd, A.Prescott, G.Segal, and D.M.van Aalten (2010).
Molecular mechanism of elongation factor 1A inhibition by a Legionella pneumophila glycosyltransferase.
  Biochem J, 426, 281-292.
PDB codes: 2wzf 2wzg
19622749 P.Tumbale, and K.Brew (2009).
Characterization of a metal-independent CAZy family 6 glycosyltransferase from Bacteroides ovatus.
  J Biol Chem, 284, 25126-25134.  
18047841 B.A.Macher, and U.Galili (2008).
The Galalpha1,3Galbeta1,4GlcNAc-R (alpha-Gal) epitope: a carbohydrate of unique evolution and clinical relevance.
  Biochim Biophys Acta, 1780, 75-88.  
18627619 C.J.Zea, G.Camci-Unal, and N.L.Pohl (2008).
Thermodynamics of binding of divalent magnesium and manganese to uridine phosphates: implications for diabetes-related hypomagnesaemia and carbohydrate biocatalysis.
  Chem Cent J, 2, 15.  
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.  
18557833 O.A.Zabotina, W.T.van de Ven, G.Freshour, G.Drakakaki, D.Cavalier, G.Mouille, M.G.Hahn, K.Keegstra, and N.V.Raikhel (2008).
Arabidopsis XXT5 gene encodes a putative alpha-1,6-xylosyltransferase that is involved in xyloglucan biosynthesis.
  Plant J, 56, 101-115.  
18394902 T.Jank, and K.Aktories (2008).
Structure and mode of action of clostridial glucosylating toxins: the ABCD model.
  Trends Microbiol, 16, 222-229.  
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.  
17465952 B.Hosseini-Maaf, J.A.Letts, M.Persson, E.Smart, P.Y.LePennec, H.Hustinx, Z.Zhao, M.M.Palcic, S.V.Evans, M.A.Chester, and M.L.Olsson (2007).
Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase.
  Transfusion, 47, 864-875.
PDB code: 2i7b
17194757 C.Koike, M.Uddin, D.E.Wildman, E.A.Gray, M.Trucco, T.E.Starzl, and M.Goodman (2007).
Functionally important glycosyltransferase gain and loss during catarrhine primate emergence.
  Proc Natl Acad Sci U S A, 104, 559-564.  
17603109 G.Devasahayam, D.J.Burke, and T.W.Sturgill (2007).
Golgi manganese transport is required for rapamycin signaling in Saccharomyces cerevisiae.
  Genetics, 177, 231-238.  
17642512 J.A.Letts, M.Persson, B.Schuman, S.N.Borisova, M.M.Palcic, and S.V.Evans (2007).
The effect of heavy atoms on the conformation of the active-site polypeptide loop in human ABO(H) blood-group glycosyltransferase B.
  Acta Crystallogr D Biol Crystallogr, 63, 860-865.
PDB codes: 2pgv 2pgy
17220972 L.L.Lairson, W.W.Wakarchuk, and S.G.Withers (2007).
Alternative donor substrates for inverting and retaining glycosyltransferases.
  Chem Commun (Camb), (), 365-367.  
17259183 M.Persson, J.A.Letts, B.Hosseini-Maaf, S.N.Borisova, M.M.Palcic, S.V.Evans, and M.L.Olsson (2007).
Structural effects of naturally occurring human blood group B galactosyltransferase mutations adjacent to the DXD motif.
  J Biol Chem, 282, 9564-9570.
PDB codes: 2o1f 2o1g 2o1h
17574762 P.Molina, R.M.Knegtel, and B.A.Macher (2007).
Site-directed mutagenesis of glutamate 317 of bovine alpha-1,3Galactosyltransferase and its effect on enzyme activity: implications for reaction mechanism.
  Biochim Biophys Acta, 1770, 1266-1273.  
17901056 T.Jank, T.Giesemann, and K.Aktories (2007).
Clostridium difficile glucosyltransferase toxin B-essential amino acids for substrate binding.
  J Biol Chem, 282, 35222-35231.  
17850743 Y.Zhang, Y.Xiang, J.L.Van Etten, and M.G.Rossmann (2007).
Structure and function of a chlorella virus-encoded glycosyltransferase.
  Structure, 15, 1031-1039.
PDB codes: 2p6w 2p72 2p73
16923820 A.Blume, J.Angulo, T.Biet, H.Peters, A.J.Benie, M.Palcic, and T.Peters (2006).
Fragment-based screening of the donor substrate specificity of human blood group B galactosyltransferase using saturation transfer difference NMR.
  J Biol Chem, 281, 32728-32740.  
16829524 J.E.Pak, P.Arnoux, S.Zhou, P.Sivarajah, M.Satkunarajah, X.Xing, and J.M.Rini (2006).
X-ray crystal structure of leukocyte type core 2 beta1,6-N-acetylglucosaminyltransferase. Evidence for a convergence of metal ion-independent glycosyltransferase mechanism.
  J Biol Chem, 281, 26693-26701.
PDB codes: 2gak 2gam
17176435 J.Milland, and M.S.Sandrin (2006).
ABO blood group and related antigens, natural antibodies and transplantation.
  Tissue Antigens, 68, 459-466.  
17057723 L.L.Lairson, A.G.Watts, W.W.Wakarchuk, and S.G.Withers (2006).
Using substrate engineering to harness enzymatic promiscuity and expand biological catalysis.
  Nat Chem Biol, 2, 724-728.  
16007668 C.J.Zea, and N.L.Pohl (2005).
Unusual sugar nucleotide recognition elements of mesophilic vs. thermophilic glycogen synthases.
  Biopolymers, 79, 106-113.  
15987364 M.H.Yazer, G.A.Denomme, N.L.Rose, and M.M.Palcic (2005).
Amino-acid substitution in the disordered loop of blood group B-glycosyltransferase enzyme causes weak B phenotype.
  Transfusion, 45, 1178-1182.  
15653326 P.K.Qasba, B.Ramakrishnan, and E.Boeggeman (2005).
Substrate-induced conformational changes in glycosyltransferases.
  Trends Biochem Sci, 30, 53-62.  
15849187 T.D.Hurley, S.Stout, E.Miner, J.Zhou, and P.J.Roach (2005).
Requirements for catalysis in mammalian glycogenin.
  J Biol Chem, 280, 23892-23899.
PDB codes: 1zct 1zcu 1zcv 1zcy 1zdf 1zdg
15569071 D.Cho, S.H.Kim, C.S.Ki, K.L.Choi, Y.G.Cho, J.W.Song, J.H.Shin, S.P.Suh, M.H.Yazer, and D.W.Ryang (2004).
A novel B(var) allele (547 G>A) demonstrates differential expression depending on the co-inherited ABO allele.
  Vox Sang, 87, 187-189.  
15075344 L.L.Lairson, C.P.Chiu, H.D.Ly, S.He, W.W.Wakarchuk, N.C.Strynadka, and S.G.Withers (2004).
Intermediate trapping on a mutant retaining alpha-galactosyltransferase identifies an unexpected aspartate residue.
  J Biol Chem, 279, 28339-28344.
PDB code: 1ss9
15148316 M.L.Rosén, M.Edman, M.Sjöström, and A.Wieslander (2004).
Recognition of fold and sugar linkage for glycosyltransferases by multivariate sequence analysis.
  J Biol Chem, 279, 38683-38692.  
15467186 N.Nakamura, K.Katano, S.Toba, and A.Kurosaka (2004).
Characterization of a novel polypeptide N-acetylgalactosaminyltransferase (dGalNAc-T3) from Drosophila.
  Biol Pharm Bull, 27, 1509-1514.  
14570926 R.P.Gibson, C.A.Tarling, S.Roberts, S.G.Withers, and G.J.Davies (2004).
The donor subsite of trehalose-6-phosphate synthase: binary complexes with UDP-glucose and UDP-2-deoxy-2-fluoro-glucose at 2 A resolution.
  J Biol Chem, 279, 1950-1955.
PDB codes: 1uqt 1uqu
15486088 T.A.Fritz, J.H.Hurley, L.B.Trinh, J.Shiloach, and L.A.Tabak (2004).
The beginnings of mucin biosynthesis: the crystal structure of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-T1.
  Proc Natl Acad Sci U S A, 101, 15307-15312.
PDB code: 1xhb
14752117 Y.D.Lobsanov, P.A.Romero, B.Sleno, B.Yu, P.Yip, A.Herscovics, and P.L.Howell (2004).
Structure of Kre2p/Mnt1p: a yeast alpha1,2-mannosyltransferase involved in mannoprotein biosynthesis.
  J Biol Chem, 279, 17921-17931.
PDB codes: 1s4n 1s4o 1s4p
14646108 C.Horcajada, E.Cid, J.J.Guinovart, N.Verdaguer, and J.C.Ferrer (2003).
Crystallization and preliminary X-ray analysis of the glycogen synthase from Pyrococcus abyssi.
  Acta Crystallogr D Biol Crystallogr, 59, 2322-2324.  
12493821 C.J.Phelps, C.Koike, T.D.Vaught, J.Boone, K.D.Wells, S.H.Chen, S.Ball, S.M.Specht, I.A.Polejaeva, J.A.Monahan, P.M.Jobst, S.B.Sharma, A.E.Lamborn, A.S.Garst, M.Moore, A.J.Demetris, W.A.Rudert, R.Bottino, S.Bertera, M.Trucco, T.E.Starzl, Y.Dai, and D.L.Ayares (2003).
Production of alpha 1,3-galactosyltransferase-deficient pigs.
  Science, 299, 411-414.  
12562774 L.C.Pedersen, J.Dong, F.Taniguchi, H.Kitagawa, J.M.Krahn, L.G.Pedersen, K.Sugahara, and M.Negishi (2003).
Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis.
  J Biol Chem, 278, 14420-14428.
PDB codes: 1omx 1omz 1on6 1on8
12538870 Y.Hu, L.Chen, S.Ha, B.Gross, B.Falcone, D.Walker, M.Mokhtarzadeh, and S.Walker (2003).
Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases.
  Proc Natl Acad Sci U S A, 100, 845-849.
PDB code: 1nlm
14500887 Z.Zhang, S.Kochhar, and M.Grigorov (2003).
Exploring the sequence-structure protein landscape in the glycosyltransferase family.
  Protein Sci, 12, 2291-2302.  
12032363 A.Faik, N.J.Price, N.V.Raikhel, and K.Keegstra (2002).
An Arabidopsis gene encoding an alpha-xylosyltransferase involved in xyloglucan biosynthesis.
  Proc Natl Acad Sci U S A, 99, 7797-7802.  
12023287 A.Hellberg, J.Poole, and M.L.Olsson (2002).
Molecular basis of the globoside-deficient P(k) blood group phenotype. Identification of four inactivating mutations in the UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase gene.
  J Biol Chem, 277, 29455-29459.  
11896059 C.Wang, M.Risteli, J.Heikkinen, A.K.Hussa, L.Uitto, and R.Myllyla (2002).
Identification of amino acids important for the catalytic activity of the collagen glucosyltransferase associated with the multifunctional lysyl hydroxylase 3 (LH3).
  J Biol Chem, 277, 18568-18573.  
12011052 E.Boix, Y.Zhang, G.J.Swaminathan, K.Brew, and K.R.Acharya (2002).
Structural basis of ordered binding of donor and acceptor substrates to the retaining glycosyltransferase, alpha-1,3-galactosyltransferase.
  J Biol Chem, 277, 28310-28318.
PDB codes: 1gwv 1gww 1gx0 1gx4
11784313 H.Ihara, Y.Ikeda, S.Koyota, T.Endo, K.Honke, and N.Taniguchi (2002).
A catalytically inactive beta 1,4-N-acetylglucosaminyltransferase III (GnT-III) behaves as a dominant negative GnT-III inhibitor.
  Eur J Biochem, 269, 193-201.  
12235155 J.Stolz, and S.Munro (2002).
The components of the Saccharomyces cerevisiae mannosyltransferase complex M-Pol I have distinct functions in mannan synthesis.
  J Biol Chem, 277, 44801-44808.  
11986319 M.Ouzzine, S.Gulberti, N.Levoin, P.Netter, J.Magdalou, and S.Fournel-Gigleux (2002).
The donor substrate specificity of the human beta 1,3-glucuronosyltransferase I toward UDP-glucuronic acid is determined by two crucial histidine and arginine residues.
  J Biol Chem, 277, 25439-25445.  
12199709 M.Tenno, S.Toba, F.J.Kézdy, A.P.Elhammer, and A.Kurosaka (2002).
Identification of two cysteine residues involved in the binding of UDP-GalNAc to UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 1 (GalNAc-T1).
  Eur J Biochem, 269, 4308-4316.  
11943783 P.E.Pummill, and P.L.DeAngelis (2002).
Evaluation of critical structural elements of UDP-sugar substrates and certain cysteine residues of a vertebrate hyaluronan synthase.
  J Biol Chem, 277, 21610-21616.  
11807274 R.P.Gibson, R.M.Lloyd, S.J.Charnock, and G.J.Davies (2002).
Characterization of Escherichia coli OtsA, a trehalose-6-phosphate synthase from glycosyltransferase family 20.
  Acta Crystallogr D Biol Crystallogr, 58, 349-351.  
12198488 S.I.Patenaude, N.O.Seto, S.N.Borisova, A.Szpacenko, S.L.Marcus, M.M.Palcic, and S.V.Evans (2002).
The structural basis for specificity in human ABO(H) blood group biosynthesis.
  Nat Struct Biol, 9, 685-690.
PDB codes: 1lz0 1lz7 1lzi 1lzj
  11592969 E.Boix, G.J.Swaminathan, Y.Zhang, R.Natesh, K.Brew, and K.R.Acharya (2001).
Structure of UDP complex of UDP-galactose:beta-galactoside-alpha -1,3-galactosyltransferase at 1.53-A resolution reveals a conformational change in the catalytically important C terminus.
  J Biol Chem, 276, 48608-48614.
PDB code: 1k4v
11606199 P.Petrová, J.Koca, and A.Imberty (2001).
Molecular dynamics simulations of solvated UDP-glucose in interaction with Mg2+ cations.
  Eur J Biochem, 268, 5365-5374.  
11717264 V.Chazalet, K.Uehara, R.A.Geremia, and C.Breton (2001).
Identification of essential amino acids in the Azorhizobium caulinodans fucosyltransferase NodZ.
  J Bacteriol, 183, 7067-7075.  
11785761 Y.Bourne, and B.Henrissat (2001).
Glycoside hydrolases and glycosyltransferases: families and functional modules.
  Curr Opin Struct Biol, 11, 593-600.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.