7D5C

IleRS in complex with a tRNA site inhibitor

7D5C の概要

• エントリーDOI: 10.2210/pdb7d5c/pdb
• 分子名称: Isoleucine--tRNA ligase, cytoplasmic, (2E,4S,5S,6E,8E)-10-[(2S,3R,6S,8R,9S)-3-butyl-9-methyl-2-[(1E,3E)-3-methyl-5-oxidanyl-5-oxidanylidene-penta-1,3-dienyl]-3-(4-oxidanyl-4-oxidanylidene-butanoyl)oxy-1,7-dioxaspiro[5.5]undecan-8-yl]-4,8-dimethyl-5-oxidanyl-deca-2,6,8-trienoic acid, [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] (2S,3S)-2-azanyl-3-methyl-pentanoate, ... (5 entities in total)
• 機能のキーワード: trna synthetase, ligase-inhibitor complex, ligase/inhibitor
• 由来する生物種: Saccharomyces cerevisiae S288c (Baker's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 115414.30

構造登録者

Chen, B.,Luo, S.,Zhou, H. (登録日: 2020-09-25, 公開日: 2021-02-24, 最終更新日: 2023-11-29)

主引用文献

Chen, B.,Luo, S.,Zhang, S.,Ju, Y.,Gu, Q.,Xu, J.,Yang, X.L.,Zhou, H.
Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase.
Nat Commun, 12:1616-1616, 2021

PubMed Abstract: The polyketide natural product reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). Herein, a co-crystal structure suggests that the RM-A molecule occupies the substrate tRNA binding site of Saccharomyces cerevisiae IleRS (ScIleRS), by partially mimicking the binding of tRNA. RM-A binding is facilitated by the copurified intermediate product isoleucyl-adenylate (Ile-AMP). The binding assays confirm that RM-A competes with tRNA while binding synergistically with L-isoleucine or intermediate analogue Ile-AMS to the aminoacylation pocket of ScIleRS. This study highlights that the vast tRNA binding site of the Rossmann-fold catalytic domain of class I aminoacyl-tRNA synthetases could be targeted by a small molecule. This finding will inform future rational drug design.

PubMed: 33712620
DOI: 10.1038/s41467-021-21902-0

実験手法

X-RAY DIFFRACTION (1.895 Å)