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Transferase/antibiotic PDB id
1rrv
Jmol
Contents
Protein chains
401 a.a. *
Ligands
MLU-OMZ-ASN-GHP-
GHP-OMY-3FG ×2
TYD ×2
GOL ×3
BGC ×2
Metals
__K ×2
Waters ×500
* Residue conservation analysis
PDB id:
1rrv
Name: Transferase/antibiotic
Title: X-ray crystal structure of tdp-vancosaminyltransferase gtfd complex with tdp and the natural substrate, desvancosaminyl vancomycin.
Structure: Glycosyltransferase gtfd. Chain: a, b. Engineered: yes. Desvancosaminyl vancomycin. Chain: c, d
Source: Amycolatopsis orientalis. Organism_taxid: 31958. Gene: gtfd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Organism_taxid: 31958
Resolution:
2.00Å     R-factor:   0.210     R-free:   0.252
Authors: A.M.Mulichak,W.Lu,H.C.Losey,C.T.Walsh,R.M.Garavito
Key ref:
A.M.Mulichak et al. (2004). Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands. Biochemistry, 43, 5170-5180. PubMed id: 15122882 DOI: 10.1021/bi036130c
Date:
09-Dec-03     Release date:   18-May-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9AFC7  (Q9AFC7_AMYOR) -  Glycosyltransferase GtfD
Seq:
Struc: 		408 a.a.
401 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   3 terms 
  Biochemical function     transferase activity     2 terms  

 

 
DOI no: 10.1021/bi036130c Biochemistry 43:5170-5180 (2004)
PubMed id: 15122882  
 
 
Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands.
A.M.Mulichak, W.Lu, H.C.Losey, C.T.Walsh, R.M.Garavito.
 
  ABSTRACT  
 
The TDP-vancosaminyltransferase GtfD catalyzes the attachment of L-vancosamine to a monoglucosylated heptapeptide intermediate during the final stage of vancomycin biosynthesis. Glycosyltransferases from this and similar antibiotic pathways are potential tools for the design of new compounds that are effective against vancomycin resistant bacterial strains. We have determined the X-ray crystal structure of GtfD as a complex with TDP and the natural glycopeptide substrate at 2.0 A resolution. GtfD, a member of the bidomain GT-B glycosyltransferase superfamily, binds TDP in the interdomain cleft, while the aglycone acceptor binds in a deep crevice in the N-terminal domain. However, the two domains are more interdependent in terms of substrate binding and overall structure than was evident in the structures of closely related glycosyltransferases GtfA and GtfB. Structural and kinetic analyses support the identification of Asp13 as a catalytic general base, with a possible secondary role for Thr10. Several residues have also been identified as being involved in donor sugar binding and recognition.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21513888 J.Härle, S.Günther, B.Lauinger, M.Weber, B.Kammerer, D.L.Zechel, A.Luzhetskyy, and A.Bechthold (2011).
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  J Bacteriol, 191, 2871-2875.  
19549605 A.W.Truman, M.V.Dias, S.Wu, T.L.Blundell, F.Huang, and J.B.Spencer (2009).
Chimeric glycosyltransferases for the generation of hybrid glycopeptides.
  Chem Biol, 16, 676-685.
PDB codes: 3h4i 3h4t
19389626 R.Shi, S.S.Lamb, B.Zakeri, A.Proteau, Q.Cui, T.Sulea, A.Matte, G.D.Wright, and M.Cygler (2009).
Structure and function of the glycopeptide N-methyltransferase MtfA, a tool for the biosynthesis of modified glycopeptide antibiotics.
  Chem Biol, 16, 401-410.
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19126547 Y.L.Chen, Y.H.Chen, Y.C.Lin, K.C.Tsai, and H.T.Chiu (2009).
Functional characterization and substrate specificity of spinosyn rhamnosyltransferase by in vitro reconstitution of spinosyn biosynthetic enzymes.
  J Biol Chem, 284, 7352-7363.  
18502788 A.S.Patana, M.Kurkela, M.Finel, and A.Goldman (2008).
Mutation analysis in UGT1A9 suggests a relationship between substrate and catalytic residues in UDP-glucuronosyltransferases.
  Protein Eng Des Sel, 21, 537-543.  
  19058170 C.J.Thibodeaux, C.E.Melançon, and H.W.Liu (2008).
Natural-product sugar biosynthesis and enzymatic glycodiversification.
  Angew Chem Int Ed Engl, 47, 9814-9859.  
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.  
18721755 C.Zhang, E.Bitto, R.D.Goff, S.Singh, C.A.Bingman, B.R.Griffith, C.Albermann, G.N.Phillips, and J.S.Thorson (2008).
Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis.
  Chem Biol, 15, 842-853.
PDB codes: 3d0q 3d0r
18678278 G.J.Williams, R.W.Gantt, and J.S.Thorson (2008).
The impact of enzyme engineering upon natural product glycodiversification.
  Curr Opin Chem Biol, 12, 556-564.  
18311744 K.Yokoyama, Y.Yamamoto, F.Kudo, and T.Eguchi (2008).
Involvement of two distinct N-acetylglucosaminyltransferases and a dual-function deacetylase in neomycin biosynthesis.
  Chembiochem, 9, 865-869.  
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.  
17268612 C.Hertweck, A.Luzhetskyy, Y.Rebets, and A.Bechthold (2007).
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17460661 C.J.Thibodeaux, C.E.Melançon, and H.W.Liu (2007).
Unusual sugar biosynthesis and natural product glycodiversification.
  Nature, 446, 1008-1016.  
17475008 C.Li, and Q.Wu (2007).
Adaptive evolution of multiple-variable exons and structural diversity of drug-metabolizing enzymes.
  BMC Evol Biol, 7, 69.  
17376874 D.N.Bolam, S.Roberts, M.R.Proctor, J.P.Turkenburg, E.J.Dodson, C.Martinez-Fleites, M.Yang, B.G.Davis, G.J.Davies, and H.J.Gilbert (2007).
The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity.
  Proc Natl Acad Sci U S A, 104, 5336-5341.
PDB codes: 2iya 2iyf
17828251 G.J.Williams, C.Zhang, and J.S.Thorson (2007).
Expanding the promiscuity of a natural-product glycosyltransferase by directed evolution.
  Nat Chem Biol, 3, 657-662.  
17251184 H.Y.Sun, S.W.Lin, T.P.Ko, J.F.Pan, C.L.Liu, C.N.Lin, A.H.Wang, and C.H.Lin (2007).
Structure and mechanism of Helicobacter pylori fucosyltransferase. A basis for lipopolysaccharide variation and inhibitor design.
  J Biol Chem, 282, 9973-9982.
PDB codes: 2nzw 2nzx 2nzy
18077347 M.Brazier-Hicks, W.A.Offen, M.C.Gershater, T.J.Revett, E.K.Lim, D.J.Bowles, G.J.Davies, and R.Edwards (2007).
Characterization and engineering of the bifunctional N- and O-glucosyltransferase involved in xenobiotic metabolism in plants.
  Proc Natl Acad Sci U S A, 104, 20238-20243.
PDB codes: 2vce 2vch 2vcu 2vg8
17442341 M.J.Miley, A.K.Zielinska, J.E.Keenan, S.M.Bratton, A.Radominska-Pandya, and M.R.Redinbo (2007).
Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7.
  J Mol Biol, 369, 498-511.
PDB code: 2o6l
16669774 D.Bowles, E.K.Lim, B.Poppenberger, and F.E.Vaistij (2006).
Glycosyltransferases of lipophilic small molecules.
  Annu Rev Plant Biol, 57, 567-597.  
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
16855251 M.N.Hung, E.Rangarajan, C.Munger, G.Nadeau, T.Sulea, and A.Matte (2006).
Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis.
  J Bacteriol, 188, 5606-5617.
PDB codes: 2fs5 2ft0
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
16880973 A.Luzhetskyy, A.Vente, and A.Bechthold (2005).
Glycosyltransferases involved in the biosynthesis of biologically active natural products that contain oligosaccharides.
  Mol Biosyst, 1, 117-126.  
16007668 C.J.Zea, and N.L.Pohl (2005).
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  Biopolymers, 79, 106-113.  
15980457 P.Kamra, R.S.Gokhale, and D.Mohanty (2005).
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  Nucleic Acids Res, 33, W220-W225.  
16311633 T.Bililign, B.R.Griffith, and J.S.Thorson (2005).
Structure, activity, synthesis and biosynthesis of aryl-C-glycosides.
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15911373 W.Lu, C.Leimkuhler, G.J.Gatto, R.G.Kruger, M.Oberthür, D.Kahne, and C.T.Walsh (2005).
AknT is an activating protein for the glycosyltransferase AknS in L-aminodeoxysugar transfer to the aglycone of aclacinomycin A.
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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.