1Q4W

CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2,6-DIAMINO-3H-QUINAZOLIN-4-ONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.171 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Crystallographic Study of Inhibitors of tRNA-guanine Transglycosylase Suggests a New Structure-based Pharmacophore for Virtual Screening.

Brenk, R.Meyer, E.Reuter, K.Stubbs, M.T.Garcia, G.A.Diederich, F.Klebe, G.

(2004) J Mol Biol 338: 55-75

  • DOI: https://doi.org/10.1016/j.jmb.2004.02.019
  • Primary Citation of Related Structures:  
    1Q4W, 1Q63, 1Q65, 1Q66, 1R5Y

  • PubMed 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.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Queuine tRNA-ribosyltransferase386Zymomonas mobilisMutation(s): 0 
Gene Names: TGT
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
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DQU
Query on DQU

Download Ideal Coordinates CCD File 
C [auth A]2,6-DIAMINO-3H-QUINAZOLIN-4-ONE
C8 H8 N4 O
YCRCNZBZUQLULA-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DQU Binding MOAD:  1Q4W Ki: 350 (nM) from 1 assay(s)
PDBBind:  1Q4W Ki: 350 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.171 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.35α = 90
b = 65.33β = 96.1
c = 70.16γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-04-13
    Type: Initial release
  • Version 1.1: 2008-04-29
    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: 2023-08-16
    Changes: Advisory, Data collection, Database references, Refinement description