1Q65

CRYSTAL STRUCTURE OF TGT IN COMPLEX WITH 2,6-DIAMINO-8-(2-dimethylaminoethylsulfanylmethyl)-3H-QUINAZOLIN-4-ONE crystallized at pH 5.5

1Q65 の概要

• エントリーDOI: 10.2210/pdb1q65/pdb
• 関連するPDBエントリー: 1pud 1Q4W 1Q63 1Q66
• 分子名称: Queuine tRNA-ribosyltransferase, ZINC ION, 2,6-DIAMINO-8-(2-DIMETHYLAMINOETHYLSULFANYLMETHYL)-3H-QUINAZOLIN-4-ONE, ... (4 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Zymomonas mobilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43284.50

構造登録者

Brenk, R.,Meyer, E.,Reuter, K.,Stubbs, M.T.,Garcia, G.A.,Klebe, G. (登録日: 2003-08-12, 公開日: 2004-04-13, 最終更新日: 2023-08-16)

主引用文献

Brenk, R.,Meyer, E.,Reuter, K.,Stubbs, M.T.,Garcia, G.A.,Diederich, F.,Klebe, G.
Crystallographic Study of Inhibitors of tRNA-guanine Transglycosylase Suggests a New Structure-based Pharmacophore for Virtual Screening.
J.Mol.Biol., 338:55-75, 2004

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.

PubMed: 15050823
DOI: 10.1016/j.jmb.2004.02.019

実験手法

X-RAY DIFFRACTION (2.1 Å)