8POT

Ternary complex of E. coli leucyl-tRNA synthetase, tRNA(leu) and the benzoxaborole cmpd9 in the editing conformation

8POT の概要

• エントリーDOI: 10.2210/pdb8pot/pdb
• 関連するPDBエントリー: 8POQ 8POR 8POS
• 分子名称: Leucine--tRNA ligase, tRNA(leu), 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: leucine trna ligase, atp binding protein, trna aminoacylation for protein translation, cytosolic reaction catalysed: atp + l-leucine + trna(leu) = amp + diphosphate + l-leucyl-trna(leu), ligase
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 128440.12

構造登録者

Palencia, A.,Hoffmann, G. (登録日: 2023-07-05, 公開日: 2024-06-12, 最終更新日: 2024-07-24)

主引用文献

Hoffmann, G.,Lukarska, M.,Clare, R.H.,Masters, E.K.G.,Johnston, K.L.,Ford, L.,Turner, J.D.,Ward, S.A.,Taylor, M.J.,Jensen, M.R.,Palencia, A.
Targeting a microbiota Wolbachian aminoacyl-tRNA synthetase to block its pathogenic host.
Sci Adv, 10:eado1453-eado1453, 2024

PubMed Abstract: The interplay between humans and their microbiome is crucial for various physiological processes, including nutrient absorption, immune defense, and maintaining homeostasis. Microbiome alterations can directly contribute to diseases or heighten their likelihood. This relationship extends beyond humans; microbiota play vital roles in other organisms, including eukaryotic pathogens causing severe diseases. Notably, , a bacterial microbiota, is essential for parasitic worms responsible for lymphatic filariasis and onchocerciasis, devastating human illnesses. Given the lack of rapid cures for these infections and the limitations of current treatments, new drugs are imperative. Here, we disrupt 's symbiosis with pathogens using boron-based compounds targeting an unprecedented enzyme, leucyl-tRNA synthetase (LeuRS), effectively inhibiting its growth. Through a compound demonstrating anti- efficacy in infected cells, we use biophysical experiments and x-ray crystallography to elucidate the mechanism behind LeuRS inhibition. We reveal that these compounds form adenosine-based adducts inhibiting protein synthesis. Overall, our study underscores the potential of disrupting key microbiota to control infections.

PubMed: 38985862
DOI: 10.1126/sciadv.ado1453

実験手法

X-RAY DIFFRACTION (2.149 Å)