1q66
CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2-AMINO-6-AMINOMETHYL-8-phenylsulfanylmethyl-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5
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| , resolution 1.75Å | |||||||
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| Ligands: | and | ||||||
| Gene: | TGT (Zymomonas mobilis) | ||||||
| Activity: | Queuine tRNA-ribosyltransferase, with EC number 2.4.2.29 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
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 StructureAbout this Structure
1Q66 is a Single protein structure of sequence from Zymomonas mobilis. Full crystallographic information is available from OCA.
ReferenceReference
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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