4HWP

Crystal structure of E. coli Threonyl-tRNA synthetase bound to a novel inhibitor

4HWP の概要

• エントリーDOI: 10.2210/pdb4hwp/pdb
• 関連するPDBエントリー: 4HWO 4HWR 4HWS 4HWT
• 分子名称: Threonine--tRNA ligase, ZINC ION, N-{[3-(4-amino-2-methylquinazolin-7-yl)phenyl]sulfonyl}-L-threoninamide, ... (4 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, protein-inhibitor complex, antibacterial, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0A8M3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96958.94

構造登録者

Hilgers, M.T. (登録日: 2012-11-08, 公開日: 2013-09-18, 最終更新日: 2024-02-28)

主引用文献

Teng, M.,Hilgers, M.T.,Cunningham, M.L.,Borchardt, A.,Locke, J.B.,Abraham, S.,Haley, G.,Kwan, B.P.,Hall, C.,Hough, G.W.,Shaw, K.J.,Finn, J.
Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design.
J.Med.Chem., 56:1748-1760, 2013

PubMed Abstract: A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.

PubMed: 23362938
DOI: 10.1021/jm301756m

実験手法

X-RAY DIFFRACTION (1.807 Å)