4ZT7

Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor N-[(4R)-6,8-dichloro-1,2,3,4-tetrahydroquinolin-4-yl]-N'-(5-fluoro-3H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine (Chem 1717)

4ZT7 の概要

• エントリーDOI: 10.2210/pdb4zt7/pdb
• 関連するPDBエントリー: 4ZT2 4ZT3 4ZT4 4ZT5 4ZT6
• 分子名称: Methionyl-tRNA synthetase, METHIONINE, DIMETHYL SULFOXIDE, ... (6 entities in total)
• 機能のキーワード: ligase, aminoacyl-trna synthetase, aars, metrs, trypanosoma brucei, protein-inhibitor complex, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Trypanosoma brucei brucei
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123832.54

構造登録者

Koh, C.-Y.,Hol, W.G.J. (登録日: 2015-05-14, 公開日: 2016-05-04, 最終更新日: 2024-11-13)

主引用文献

Zhang, Z.,Koh, C.Y.,Ranade, R.M.,Shibata, S.,Gillespie, J.R.,Hulverson, M.A.,Huang, W.,Nguyen, J.,Pendem, N.,Gelb, M.H.,Verlinde, C.L.,Hol, W.G.,Buckner, F.S.,Fan, E.
5-Fluoroimidazo[4,5-b]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors.
Acs Infect Dis., 2:399-404, 2016

PubMed Abstract: Fluorination is a well-known strategy for improving the bioavailability of drug molecules. However, its impact on efficacy is not easily predicted. On the basis of inhibitor-bound protein crystal structures, we found a beneficial fluorination spot for inhibitors targeting methionyl-tRNA synthetase of Trypanosoma brucei. In particular, incorporating 5-fluoroimidazo[4,5-b]pyridine into inhibitors leads to central nervous system bioavailability and maintained or even improved efficacy.

PubMed: 27627628
DOI: 10.1021/acsinfecdis.6b00036

実験手法

X-RAY DIFFRACTION (2.4 Å)