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PDBsum entry 1lzi

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protein ligands metals links
Transferase PDB id
1lzi
Jmol
Contents
Protein chain
264 a.a. *
Ligands
FUC-BHG
UDP
Metals
_HG ×5
_MN
Waters ×394
* Residue conservation analysis
PDB id:
1lzi
Name: Transferase
Title: Glycosyltransferase a + udp + h antigen acceptor
Structure: Glycosyltransferase a. Chain: a. Fragment: catalytic domain, (residues 64-354). Synonym: fucosylglycoprotein alpha-n-acetylgalactosaminyltr engineered: yes. Other_details: n-terminal truncation
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.35Å     R-factor:   0.179     R-free:   0.200
Authors: S.I.Patenaude,N.O.L.Seto,S.N.Borisova,A.Szpacenko,S.L.Marcus M.M.Palcic,S.V.Evans
Key ref:
S.I.Patenaude et al. (2002). The structural basis for specificity in human ABO(H) blood group biosynthesis. Nat Struct Biol, 9, 685-690. PubMed id: 12198488 DOI: 10.1038/nsb832
Date:
10-Jun-02     Release date:   28-Aug-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P16442  (BGAT_HUMAN) -  Histo-blood group ABO system transferase
Seq:
Struc:
354 a.a.
264 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.2.4.1.37  - 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
UDP-alpha-D-galactose
+
alpha-L-fucosyl-(1->2)-D-galactosyl-R
Bound ligand (Het Group name = BHG)
matches with 64.00% similarity
=
UDP
Bound ligand (Het Group name = UDP)
corresponds exactly
+ alpha-D-galactosyl-(1->3)-(alpha-L-fucosyl-(1->2))-D-galactosyl-R
   Enzyme class 2: E.C.2.4.1.40  - 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
UDP-N-acetyl-alpha-beta-D-galactosamine
+ glycoprotein-alpha-L-fucosyl- (1->2)-D-galactose
=
UDP
Bound ligand (Het Group name = UDP)
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  

 

 
    reference    
 
 
DOI no: 10.1038/nsb832 Nat Struct Biol 9:685-690 (2002)
PubMed id: 12198488  
 
 
The structural basis for specificity in human ABO(H) blood group biosynthesis.
S.I.Patenaude, N.O.Seto, S.N.Borisova, A.Szpacenko, S.L.Marcus, M.M.Palcic, S.V.Evans.
 
  ABSTRACT  
 
The human ABO(H) blood group antigens are produced by specific glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA) uses a UDP-GalNAc donor to convert the H-antigen acceptor to the A antigen, whereas a galactosyltransferase (GTB) uses a UDP-galactose donor to convert the H-antigen acceptor to the B antigen. GTA and GTB differ only in the identity of four critical amino acid residues. Crystal structures at 1.8-1.32 A resolution of the GTA and GTB enzymes both free and in complex with disaccharide H-antigen acceptor and UDP reveal the basis for donor and acceptor specificity and show that only two of the critical amino acid residues are positioned to contact donor or acceptor substrates. Given the need for stringent stereo- and regioselectivity in this biosynthesis, these structures further demonstrate that the ability of the two enzymes to distinguish between the A and B donors is largely determined by a single amino acid residue.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. SETOR35 diagram of GTB structure. The enzymes consist of two domains separated by a wide central cleft that contains the active site where we observe UDP and the H-antigen (ball-and-stick), as well as the DXD motif (Asp 211 and Asp 213), which coordinates to the Mn2+ ion (magenta). A disordered loop consisting of residues 179 -194 lies adjacent to the active site (dotted line), separating the protein into an N-terminal polypeptide (dark blue and magenta) and C-terminal polypeptide (light blue and green). GTA and GTB differ at only four critical amino acid residue positions, Gly/Arg 176, Gly/Ser 235, Leu/Met 266 and Ala/Gly 268.
Figure 4.
Figure 4. Candidate enzyme nucleophile. Stereo view of the observed position of the acceptor, UDP and Mn2+ ion in GTB together with the modeled positions of the Gal moiety and candidate nucleophile Glu 303. GTA and GTB are 'retaining' glycosyltransferase enzymes, and transfer of donor to acceptor has been proposed to proceed through a two-step mechanism in which the donor is first transferred with inversion to a nucleophile and then transferred again with inversion to the acceptor to yield a product with conserved stereochemistry.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 685-690) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21098513 N.Soya, Y.Fang, M.M.Palcic, and J.S.Klassen (2011).
Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases.
  Glycobiology, 21, 547-552.  
20655926 B.Schuman, M.Persson, R.C.Landry, R.Polakowski, J.T.Weadge, N.O.Seto, S.N.Borisova, M.M.Palcic, and S.V.Evans (2010).
Cysteine-to-serine mutants dramatically reorder the active site of human ABO(H) blood group B glycosyltransferase without affecting activity: structural insights into cooperative substrate binding.
  J Mol Biol, 402, 399-411.
PDB codes: 3i0c 3i0d 3i0e 3i0f 3i0g 3i0h 3i0i 3i0j 3i0k 3i0l
20217221 C.Rademacher, J.Landström, N.Sindhuwinata, M.M.Palcic, G.Widmalm, and T.Peters (2010).
NMR-based exploration of the acceptor binding site of human blood group B galactosyltransferase with molecular fragments.
  Glycoconj J, 27, 349-358.  
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.  
21039577 J.R.Storry (2010).
Don't ask, don't tell: the ART of silence can jeopardize assisted pregnancies.
  Transfusion, 50, 2070-2072.  
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.  
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
19411635 D.J.Anstee (2009).
Red cell genotyping and the future of pretransfusion testing.
  Blood, 114, 248-256.  
19244233 F.Sheng, X.Jia, A.Yep, J.Preiss, and J.H.Geiger (2009).
The crystal structures of the open and catalytically competent closed conformation of Escherichia coli glycogen synthase.
  J Biol Chem, 284, 17796-17807.
PDB codes: 2qzs 2r4t 2r4u 3cop 3d1j 3guh
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.  
18513251 A.Seltsam, D.Grüger, B.Just, C.Figueiredo, C.D.Gupta, D.S.Deluca, and R.Blasczyk (2008).
Aberrant intracellular trafficking of a variant B glycosyltransferase.
  Transfusion, 48, 1898-1905.  
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.  
18192272 J.A.Alfaro, R.B.Zheng, M.Persson, J.A.Letts, R.Polakowski, Y.Bai, S.N.Borisova, N.O.Seto, T.L.Lowary, M.M.Palcic, and S.V.Evans (2008).
ABO(H) blood group A and B glycosyltransferases recognize substrate via specific conformational changes.
  J Biol Chem, 283, 10097-10108.
PDB codes: 2rit 2rix 2riy 2riz 2rj0 2rj1 2rj4 2rj5 2rj6 2rj7 2rj8 2rj9
18932014 J.Zschocke (2008).
Dominant versus recessive: molecular mechanisms in metabolic disease.
  J Inherit Metab Dis, 31, 599-618.  
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.  
19130588 S.K.Srivastava, P.R.Daggolu, S.C.Burgess, and A.R.Minerick (2008).
Dielectrophoretic characterization of erythrocytes: positive ABO blood types.
  Electrophoresis, 29, 5033-5046.  
18688480 T.Pesnot, and G.K.Wagner (2008).
Novel derivatives of UDP-glucose: concise synthesis and fluorescent properties.
  Org Biomol Chem, 6, 2884-2891.  
18564034 Y.T.Chen, M.Dejosez, T.P.Zwaka, and R.R.Behringer (2008).
H1 and H9 human embryonic stem cell lines are heterozygous for the ABO locus.
  Stem Cells Dev, 17, 853-855.  
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
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
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
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.  
16533287 A.Seltsam, C.Das Gupta, C.Bade-Doeding, and R.Blasczyk (2006).
A weak blood group A phenotype caused by a translation-initiator mutation in the ABO gene.
  Transfusion, 46, 434-440.  
16326711 J.A.Letts, N.L.Rose, Y.R.Fang, C.H.Barry, S.N.Borisova, N.O.Seto, M.M.Palcic, and S.V.Evans (2006).
Differential recognition of the type I and II H antigen acceptors by the human ABO(H) blood group A and B glycosyltransferases.
  J Biol Chem, 281, 3625-3632.
PDB codes: 1zhj 1zi1 1zi3 1zi4 1zi5 1ziz 1zj0 1zj1 1zj2 1zj3 1zjo 1zjp 2a8u 2a8w
17176435 J.Milland, and M.S.Sandrin (2006).
ABO blood group and related antigens, natural antibodies and transplantation.
  Tissue Antigens, 68, 459-466.  
16482224 W.Offen, C.Martinez-Fleites, M.Yang, E.Kiat-Lim, B.G.Davis, C.A.Tarling, C.M.Ford, D.J.Bowles, and G.J.Davies (2006).
Structure of a flavonoid glucosyltransferase reveals the basis for plant natural product modification.
  EMBO J, 25, 1396-1405.
PDB codes: 2c1x 2c1z 2c9z
17076855 Y.C.Twu, C.Y.Hsieh, and L.C.Yu (2006).
Expression of the histo-blood group B gene predominates in AB-genotype cells.
  Transfusion, 46, 1988-1996.  
16181218 A.Seltsam, and R.Blasczyk (2005).
Missense mutations outside the catalytic domain of the ABO glycosyltransferase can cause weak blood group A and B phenotypes.
  Transfusion, 45, 1663-1669.  
16007668 C.J.Zea, and N.L.Pohl (2005).
Unusual sugar nucleotide recognition elements of mesophilic vs. thermophilic glycogen synthases.
  Biopolymers, 79, 106-113.  
15475562 H.J.Lee, C.H.Barry, S.N.Borisova, N.O.Seto, R.B.Zheng, A.Blancher, S.V.Evans, and M.M.Palcic (2005).
Structural basis for the inactivity of human blood group O2 glycosyltransferase.
  J Biol Chem, 280, 525-529.
PDB codes: 1wsz 1wt0 1wt1 1wt2 1wt3 1xz6
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.  
16202060 M.L.Olsson, B.Michalewska, A.Hellberg, A.Walaszczyk, and M.A.Chester (2005).
A clue to the basis of allelic enhancement: occurrence of the Ax subgroup in the offspring of blood group O parents.
  Transfus Med, 15, 435-442.  
15701457 N.L.Pohl (2005).
Functional proteomics for the discovery of carbohydrate-related enzyme activities.
  Curr Opin Chem Biol, 9, 76-81.  
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
16157585 T.Jank, D.J.Reinert, T.Giesemann, G.E.Schulz, and K.Aktories (2005).
Change of the donor substrate specificity of Clostridium difficile toxin B by site-directed mutagenesis.
  J Biol Chem, 280, 37833-37838.  
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.  
14695527 O.O.Blumenfeld, and S.K.Patnaik (2004).
Allelic genes of blood group antigens: a source of human mutations and cSNPs documented in the Blood Group Antigen Gene Mutation Database.
  Hum Mutat, 23, 8.  
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
14617382 B.Hosseini-Maaf, A.Hellberg, M.J.Rodrigues, M.A.Chester, and M.L.Olsson (2003).
ABO exon and intron analysis in individuals with the AweakB phenotype reveals a novel O1v-A2 hybrid allele that causes four missense mutations in the A transferase.
  BMC Genet, 4, 17.  
12676935 B.Ma, G.Wang, M.M.Palcic, B.Hazes, and D.E.Taylor (2003).
C-terminal amino acids of Helicobacter pylori alpha1,3/4 fucosyltransferases determine type I and type II transfer.
  J Biol Chem, 278, 21893-21900.  
12972418 H.P.Nguyen, N.O.Seto, Y.Cai, E.K.Leinala, S.N.Borisova, M.M.Palcic, and S.V.Evans (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.
PDB codes: 1r7t 1r7u 1r7v 1r7x 1r7y 1r80 1r81 1r82
14530413 N.Sordé, G.Das, and S.Matile (2003).
Enzyme screening with synthetic multifunctional pores: focus on biopolymers.
  Proc Natl Acad Sci U S A, 100, 11964-11969.  
12529355 S.L.Marcus, R.Polakowski, N.O.Seto, E.Leinala, S.Borisova, A.Blancher, F.Roubinet, S.V.Evans, and M.M.Palcic (2003).
A single point mutation reverses the donor specificity of human blood group B-synthesizing galactosyltransferase.
  J Biol Chem, 278, 12403-12405.  
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.