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PDBsum entry 1f3e

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protein ligands metals links
Transferase PDB id
1f3e
Jmol
Contents
Protein chain
372 a.a. *
Ligands
DPZ
Metals
_ZN
Waters ×418
* Residue conservation analysis
PDB id:
1f3e
Name: Transferase
Title: A new target for shigellosis: rational design and crystallog studies of inhibitors of tRNA-guanine transglycosylase
Structure: Queuine tRNA-ribosyltransferase. Chain: a. Synonym: tRNA-guanine transglycosylase. Engineered: yes
Source: Zymomonas mobilis. Organism_taxid: 542. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.85Å     R-factor:   0.195     R-free:   0.238
Authors: U.Graedler,H.-D.Gerber,D.M.Goodenough-Lashua,G.A.G.Garcia,R. K.Reuter,M.T.Stubbs,G.Klebe
Key ref:
U.Grädler et al. (2001). A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase. J Mol Biol, 306, 455-467. PubMed id: 11178905 DOI: 10.1006/jmbi.2000.4256
Date:
02-Jun-00     Release date:   15-Jun-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28720  (TGT_ZYMMO) -  Queuine tRNA-ribosyltransferase
Seq:
Struc:
386 a.a.
372 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.29  - tRNA-guanine(34) transglycosylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. Guanine34 in tRNA + queuine = queuosine34 in tRNA + guanine
2. Guanine34 in tRNA + 7-aminomethyl-7-carbaguanine = 7-aminomethyl-7- carbaguanine34 in tRNA + guanine
Guanine(34) in tRNA
+
queuine
Bound ligand (Het Group name = DPZ)
matches with 58.82% similarity
= queuosine(34) in tRNA
+ guanine
Guanine(34) in tRNA
+
7-aminomethyl-7-carbaguanine
Bound ligand (Het Group name = DPZ)
matches with 58.82% similarity
= 7-aminomethyl-7- carbaguanine(34) in tRNA
+ guanine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     tRNA processing   3 terms 
  Biochemical function     transferase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2000.4256 J Mol Biol 306:455-467 (2001)
PubMed id: 11178905  
 
 
A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase.
U.Grädler, H.D.Gerber, D.M.Goodenough-Lashua, G.A.Garcia, R.Ficner, K.Reuter, M.T.Stubbs, G.Klebe.
 
  ABSTRACT  
 
Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hyper-modification of cognate tRNAs leading to the exchange of G34 at the wobble position in the anticodon loop by preQ1 (2-amino-5-(aminomethyl)pyrrolo[2,3-d]pyrimidin-4(3H)-one) as part of the biosynthesis of queuine (Q). Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium, revealing TGT as a new target for the design of potent drugs against Shigellosis. The X-ray structure of Zymomonas mobilis TGT in complex with preQ1 was used to search for new putative inhibitors with the computer program LUDI. An initial screen of the Available Chemical Directory, a database compiled from commercially available compounds, suggested several hits. Of these, 4-aminophthalhydrazide (APH) showed an inhibition constant in the low micromolar range. The 1.95 A crystal structure of APH in complex with Z. mobilis TGT served as a starting point for further modification of this initial lead.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Representation of the 1.95 Å resolution 2jFo j - jF c j map contoured at 1.0 s of the Z. mobilis TGT in complex with 4-aminophthalhydrazide (APH).
Figure 6.
Figure 6. Alignment of TGT crystal structure in com- plex with 3,5-DAPH (orange), 3,5-DAPH-01 (magenta), 3,5-DAPH-02 (green) and 5-ANH (blue).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 306, 455-467) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19894214 T.Ritschel, P.C.Kohler, G.Neudert, A.Heine, F.Diederich, and G.Klebe (2009).
How to Replace the Residual Solvation Shell of Polar Active Site Residues to Achieve Nanomolar Inhibition of tRNA-Guanine Transglycosylase.
  ChemMedChem, 4, 2012-2023.
PDB codes: 3eos 3eou 3gc4 3gc5 3ge7
19199329 T.Ritschel, S.Hoertner, A.Heine, F.Diederich, and G.Klebe (2009).
Crystal structure analysis and in silico pKa calculations suggest strong pKa shifts of ligands as driving force for high-affinity binding to TGT.
  Chembiochem, 10, 716-727.
PDB codes: 2z7k 3c2n 3c2y 3c2z
15916423 A.P.Graves, R.Brenk, and B.K.Shoichet (2005).
Decoys for docking.
  J Med Chem, 48, 3714-3728.
PDB code: 1xep
16247735 B.Nanduri, M.L.Lawrence, S.Vanguri, and S.C.Burgess (2005).
Proteomic analysis using an unfinished bacterial genome: the effects of subminimum inhibitory concentrations of antibiotics on Mannheimia haemolytica virulence factor expression.
  Proteomics, 5, 4852-4863.  
15951383 K.A.Todorov, X.J.Tan, S.T.Nonekowski, G.A.Garcia, and H.A.Carlson (2005).
The role of aspartic acid 143 in E. coli tRNA-guanine transglycosylase: insights from mutagenesis studies and computational modeling.
  Biophys J, 89, 1965-1977.  
15602552 B.K.Shoichet (2004).
Virtual screening of chemical libraries.
  Nature, 432, 862-865.  
12581659 A.R.Ferré-D'Amaré (2003).
RNA-modifying enzymes.
  Curr Opin Struct Biol, 13, 49-55.  
12556445 C.E.Atreya, E.F.Johnson, J.J.Irwin, A.Dow, K.M.Massimine, I.Coppens, V.Stempliuk, S.Beverley, K.A.Joiner, B.K.Shoichet, and K.S.Anderson (2003).
A molecular docking strategy identifies Eosin B as a non-active site inhibitor of protozoal bifunctional thymidylate synthase-dihydrofolate reductase.
  J Biol Chem, 278, 14092-14100.  
12909636 J.D.Kittendorf, T.Sgraja, K.Reuter, G.Klebe, and G.A.Garcia (2003).
An essential role for aspartate 264 in catalysis by tRNA-guanine transglycosylase from Escherichia coli.
  J Biol Chem, 278, 42369-42376.
PDB code: 1pxg
14523925 R.Brenk, M.T.Stubbs, A.Heine, K.Reuter, and G.Klebe (2003).
Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design.
  Chembiochem, 4, 1066-1077.
PDB codes: 1ozm 1ozq 1p0b 1p0d 1p0e
12133718 B.K.Shoichet, S.L.McGovern, B.Wei, and J.J.Irwin (2002).
Lead discovery using molecular docking.
  Curr Opin Chem Biol, 6, 439-446.  
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.