1q66
From Proteopedia
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CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5
Overview
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.
About this Structure
1Q66 is a Single protein structure of sequence from Zymomonas mobilis with and as ligands. Active as Queuine tRNA-ribosyltransferase, with EC number 2.4.2.29 Full crystallographic information is available from OCA.
Reference
Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening., Brenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich F, Klebe G, J Mol Biol. 2004 Apr 16;338(1):55-75. PMID:15050823
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