1F3E

A NEW TARGET FOR SHIGELLOSIS: RATIONAL DESIGN AND CRYSTALLOGRAPHIC STUDIES OF INHIBITORS OF TRNA-GUANINE TRANSGLYCOSYLASE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.195 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase.

Gradler, U.Gerber, H.D.Goodenough-Lashua, D.M.Garcia, G.A.Ficner, R.Reuter, K.Stubbs, M.T.Klebe, G.

(2001) J Mol Biol 306: 455-467

  • DOI: https://doi.org/10.1006/jmbi.2000.4256
  • Primary Citation of Related Structures:  
    1ENU, 1F3E

  • PubMed 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.


  • Organizational Affiliation

    Institut für Pharmazeutische Chemie, Marbacher Weg 6, Philipps-Universität Marburg, 35032, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
QUEUINE TRNA-RIBOSYLTRANSFERASE386Zymomonas mobilisMutation(s): 0 
EC: 2.4.2.29
UniProt
Find proteins for P28720 (Zymomonas mobilis subsp. mobilis (strain ATCC 31821 / ZM4 / CP4))
Explore P28720 
Go to UniProtKB:  P28720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28720
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
DPZ PDBBind:  1F3E Ki: 200 (nM) from 1 assay(s)
Binding MOAD:  1F3E Ki: 200 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.195 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.67α = 90
b = 64.94β = 96.61
c = 71.05γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-06-15
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2020-08-19
    Changes: Advisory, Data collection, Derived calculations
  • Version 1.4: 2024-02-07
    Changes: Advisory, Data collection, Database references