spacer
spacer

PDBsum entry 1n2v

Go to PDB code: 
protein ligands metals links
Transferase PDB id
1n2v
Jmol
Contents
Protein chain
372 a.a. *
Ligands
BDI
Metals
_ZN
Waters ×282
* Residue conservation analysis
PDB id:
1n2v
Name: Transferase
Title: Crystal structure of tgt in complex with 2-butyl-5,6-dihydro imidazo[4,5-d]pyridazine-4,7-dione
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:
2.10Å     R-factor:   0.188     R-free:   0.233
Authors: R.Brenk,L.Naerum,U.Graedler,H.-D.Gerber,G.A.Garcia,K.Reuter, M.T.Stubbs,G.Klebe
Key ref: R.Brenk et al. (2003). Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis. J Med Chem, 46, 1133-1143. PubMed id: 12646024 DOI: 10.1021/jm0209937
Date:
24-Oct-02     Release date:   08-Apr-03    
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 = BDI)
matches with 47.37% similarity
= queuosine(34) in tRNA
+ guanine
Guanine(34) in tRNA
+
7-aminomethyl-7-carbaguanine
Bound ligand (Het Group name = BDI)
matches with 47.37% 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: 10.1021/jm0209937 J Med Chem 46:1133-1143 (2003)
PubMed id: 12646024  
 
 
Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis.
R.Brenk, L.Naerum, U.Grädler, H.D.Gerber, G.A.Garcia, K.Reuter, M.T.Stubbs, G.Klebe.
 
  ABSTRACT  
 
Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hypermodification of cognate tRNAs, leading to the exchange of G34 by preQ1 at the wobble position in the anticodon loop. Mutation of the tgt gene in Shigella flexneri results in a significant loss of pathogenicity of the bacterium due to inefficient translation of a virulence protein mRNA. Herein, we describe the discovery of a ligand with an unexpected binding mode. On the basis of this binding mode, three slightly deviating pharmacophore hypotheses have been derived. Virtual screening based on this composite pharmacophore model retrieved a set of potential TGT inhibitors belonging to several compound classes. All nine tested inhibitors being representatives of these classes showed activity in the micromolar range, two of them even in the submicromolar range.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19908272 D.M.Krüger, and A.Evers (2010).
Comparison of structure- and ligand-based virtual screening protocols considering hit list complementarity and enrichment factors.
  ChemMedChem, 5, 148-158.  
19416920 D.G.Teotico, K.Babaoglu, G.J.Rocklin, R.S.Ferreira, A.M.Giannetti, and B.K.Shoichet (2009).
Docking for fragment inhibitors of AmpC beta-lactamase.
  Proc Natl Acad Sci U S A, 106, 7455-7460.
PDB codes: 3gqz 3gr2 3grj 3gsg 3gtc 3gv9 3gvb
19320487 N.L.Ramsden, L.Buetow, A.Dawson, L.A.Kemp, V.Ulaganathan, R.Brenk, G.Klebe, and W.N.Hunter (2009).
A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.
  J Med Chem, 52, 2531-2542.
PDB codes: 3elc 3eor 3ern 3esj 3fba
18188508 A.C.Good, and T.I.Oprea (2008).
Optimization of CAMD techniques 3. Virtual screening enrichment studies: a help or hindrance in tool selection?
  J Comput Aided Mol Des, 22, 169-178.  
18217214 C.Gerlach, H.Broughton, and A.Zaliani (2008).
FTree query construction for virtual screening: a statistical analysis.
  J Comput Aided Mol Des, 22, 111-118.  
18037921 P.Taylor, E.Blackburn, Y.G.Sheng, S.Harding, K.Y.Hsin, D.Kan, S.Shave, and M.D.Walkinshaw (2008).
Ligand discovery and virtual screening using the program LIDAEUS.
  Br J Pharmacol, 153, S55-S67.  
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
17393392 P.Block, N.Weskamp, A.Wolf, and G.Klebe (2007).
Strategies to search and design stabilizers of protein-protein interactions: a feasibility study.
  Proteins, 68, 170-186.  
16708364 E.Perola (2006).
Minimizing false positives in kinase virtual screens.
  Proteins, 64, 422-435.  
16793526 G.Klebe (2006).
Virtual ligand screening: strategies, perspectives and limitations.
  Drug Discov Today, 11, 580-594.  
16381925 P.Block, C.A.Sotriffer, I.Dramburg, and G.Klebe (2006).
AffinDB: a freely accessible database of affinities for protein-ligand complexes from the PDB.
  Nucleic Acids Res, 34, D522-D526.  
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.  
15520816 D.B.Kitchen, H.Decornez, J.R.Furr, and J.Bajorath (2004).
Docking and scoring in virtual screening for drug discovery: methods and applications.
  Nat Rev Drug Discov, 3, 935-949.  
15288245 J.C.Alvarez (2004).
High-throughput docking as a source of novel drug leads.
  Curr Opin Chem Biol, 8, 365-370.  
15288244 J.M.Jansen, and E.J.Martin (2004).
Target-biased scoring approaches and expert systems in structure-based virtual screening.
  Curr Opin Chem Biol, 8, 359-364.  
15288243 T.I.Oprea, and H.Matter (2004).
Integrating virtual screening in lead discovery.
  Curr Opin Chem Biol, 8, 349-358.  
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
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.