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Transferase PDB-id
1rrv
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PROCHECK
Protein chains
401 a.a. *
Ligands
DVV ×2
TYD ×2
GOL ×3
Metal ions
__K ×2
Waters ×500

* Residue conservation analysis
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PDB id: 1rrv
Name: Transferase
Title: X-ray crystal structure of tdp-vancosaminyltransferase gtfd as a complex with tdp and the natural substrate, desvancosaminyl vancomycin.

Structure:
Glycosyltransferase gtfd. Chain: a, b. Engineered: yes

Source:
Amycolatopsis orientalis. Organism_taxid: 31958. Gene: gtfd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

UniProt:
Chains A, B: Q9AFC7 (Q9AFC7_AMYOR)
Pfam   ArchSchema ?
Seq:
Struc:
Seq: 408 a.a.
Struc: 401 a.a.*
Key:    PfamA domain
 Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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
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    Key reference    
 
 
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
19233921 A.Ramos, C.Olano, A.F.Braña, C.Méndez, and J.A.Salas (2009).
Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis.
  J Bacteriol, 191, 2871-2875.  
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.  
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.  
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).
Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork.
  Nat Prod Rep, 24, 162-190.  
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
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).
Unusual sugar nucleotide recognition elements of mesophilic vs. thermophilic glycogen synthases.
  Biopolymers, 79, 106-113.  
15980457 P.Kamra, R.S.Gokhale, and D.Mohanty (2005).
SEARCHGTr: a program for analysis of glycosyltransferases involved in glycosylation of secondary metabolites.
  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.
  Nat Prod Rep, 22, 742-760.  
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.