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PDBsum entry 1r5y

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protein ligands metals links
Transferase PDB id
1r5y
Jmol
Contents
Protein chain
361 a.a. *
Ligands
DQU
Metals
_ZN
Waters ×415
* Residue conservation analysis
PDB id:
1r5y
Name: Transferase
Title: Crystal structure of tgt in complex with 2,6-diamino-3h-quin one crystallized at ph 5.5
Structure: Queuine tRNA-ribosyltransferase. Chain: a. Synonym: tRNA-guanine transglycosylase, guanine insertion e tgt. Engineered: yes
Source: Zymomonas mobilis. Organism_taxid: 542. Gene: tgt. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.20Å     R-factor:   0.172     R-free:   0.199
Authors: R.Brenk,E.Meyer,K.Reuter,G.A.Garcia,M.T.Stubbs,G.Klebe
Key ref:
R.Brenk et al. (2004). Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening. J Mol Biol, 338, 55-75. PubMed id: 15050823 DOI: 10.1016/j.jmb.2004.02.019
Date:
13-Oct-03     Release date:   13-Apr-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28720  (TGT_ZYMMO) -  Queuine tRNA-ribosyltransferase
Seq:
Struc:
386 a.a.
361 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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 = DQU)
matches with 73.33% similarity
= queuosine(34) in tRNA
+ guanine
Guanine(34) in tRNA
+
7-aminomethyl-7-carbaguanine
Bound ligand (Het Group name = DQU)
matches with 73.33% 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: 10.1016/j.jmb.2004.02.019 J Mol Biol 338:55-75 (2004)
PubMed id: 15050823  
 
 
Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening.
R.Brenk, E.A.Meyer, K.Reuter, M.T.Stubbs, G.A.Garcia, F.Diederich, G.Klebe.
 
  ABSTRACT  
 
The enzyme tRNA-guanine transglycosylase (TGT) is involved in the pathogenicity of Shigellae. As the crystal structure of this protein is known, it is a putative target for the structure-based design of inhibitors. Here we report a crystallographic study of several new ligands exhibiting a 2,6-diamino-3H-quinazolin-4-one scaffold, which has been shown recently to be a promising template for TGT-inhibitors. Crystal structure analysis of these complexes has revealed an unexpected movement of the side-chain of Asp102. A detailed analysis of the water network disrupted by this rotation has lead to the derivation of a new composite pharmacophore. A virtual screening has been performed based on this pharmacophore hypothesis and several new inhibitors of micromolar binding affinity with new skeletons have been discovered.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Assumed mechanism of transglycosylation catalysed by TGT. 2 Asp280 acts as nucleophile and Asp102 as general acid/base.
Figure 12.
Figure 12. Structure-based pharmacophore hypothesis (ligand 1 and protein atoms are shown for orientation). Ligand donor groups as well as the corresponding acceptor groups on the protein are coloured in blue, ligand acceptor groups as well as the corresponding donor groups on the protein are coloured in red. The hydrophobic property is indicated in green. The inter- actions to the carboxylate group of Asp156 as well as the acceptor groups Acc2a resp. Acc2b are requested in the search query as alternative options.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 338, 55-75) copyright 2004.  
  Figures were selected by an automated process.  

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
18004751 J.W.Torrance, M.W.Macarthur, and J.M.Thornton (2008).
Evolution of binding sites for zinc and calcium ions playing structural roles.
  Proteins, 71, 813-830.  
17949745 N.Tidten, B.Stengl, A.Heine, G.A.Garcia, G.Klebe, and K.Reuter (2007).
Glutamate versus glutamine exchange swaps substrate selectivity in tRNA-guanine transglycosylase: insight into the regulation of substrate selectivity by kinetic and crystallographic studies.
  J Mol Biol, 374, 764-776.
PDB codes: 2oko 2pot 2pwu 2pwv 2qii 2z1v 2z1w 2z1x
16793526 G.Klebe (2006).
Virtual ligand screening: strategies, perspectives and limitations.
  Drug Discov Today, 11, 580-594.  
16206323 B.Stengl, K.Reuter, and G.Klebe (2005).
Mechanism and substrate specificity of tRNA-guanine transglycosylases (TGTs): tRNA-modifying enzymes from the three different kingdoms of life share a common catalytic mechanism.
  Chembiochem, 6, 1926-1939.  
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.  
15782396 R.E.Cachau, and A.D.Podjarny (2005).
High-resolution crystallography and drug design.
  J Mol Recognit, 18, 196-202.  
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.