4EG3

Trypanosoma brucei methionyl-tRNA synthetase in complex with product methionyl-adenylate

4EG3 の概要

• エントリーDOI: 10.2210/pdb4eg3/pdb
• 関連するPDBエントリー: 4EG1 4EG4 4EG5 4EG6 4EG7 4EG8 4EGA
• 分子名称: Methionyl-tRNA synthetase, putative, GLYCEROL, [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] (2S)-2-azanyl-4-methylsulfanyl-butanoate, ... (4 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, aars, metrs, parasite, ligase, protein-inhibitor complex, rossmann-fold, translation, nucleotide binding, rossmann fold, trna binding atp binding
• 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: 124839.28

構造登録者

Koh, C.Y.,Kim, J.E.,Shibata, S.,Fan, E.,Verlinde, C.L.M.J.,Hol, W.G.J. (登録日: 2012-03-30, 公開日: 2012-09-12, 最終更新日: 2024-10-30)

主引用文献

Koh, C.Y.,Kim, J.E.,Shibata, S.,Ranade, R.M.,Yu, M.,Liu, J.,Gillespie, J.R.,Buckner, F.S.,Verlinde, C.L.,Fan, E.,Hol, W.G.
Distinct States of Methionyl-tRNA Synthetase Indicate Inhibitor Binding by Conformational Selection.
Structure, 20:1681-1691, 2012

PubMed Abstract: To guide development of new drugs targeting methionyl-tRNA synthetase (MetRS) for treatment of human African trypanosomiasis, crystal structure determinations of Trypanosoma brucei MetRS in complex with its substrate methionine and its intermediate product methionyl-adenylate were followed by those of the enzyme in complex with high-affinity aminoquinolone inhibitors via soaking experiments. Drastic changes in conformation of one of the two enzymes in the asymmetric unit allowed these inhibitors to occupy an enlarged methionine pocket and a new so-called auxiliary pocket. Interestingly, a small low-affinity compound caused the same conformational changes, removed the methionine without occupying the methionine pocket, and occupied the previously not existing auxiliary pocket. Analysis of these structures indicates that the binding of the inhibitors is the result of conformational selection, not induced fit.

PubMed: 22902861
DOI: 10.1016/j.str.2012.07.011

実験手法

X-RAY DIFFRACTION (2.94 Å)