1Q63: Crystal Structure Of Tgt In Complex With 2,6-Diamino-8-(1h-Imidazol-2- Ylsulfanylmethyl)-3h-Quinazoline-4-One Crystallized At Ph 5.5

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.
PDB ID: 1Q63Download
MMDB ID: 27284
PDB Deposition Date: 2003/8/12
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 1Q63: monomeric; determined by author
Molecular Components in 1Q63
Label Count Molecule
Protein (1 molecule)
Queuine tRNA-ribosyltransferase
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB