2V0C

LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A SULPHAMOYL ANALOGUE OF LEUCYL-ADENYLATE In the synthetic site and an adduct of AMP with 5-Fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690) in the editing site

2V0C の概要

• エントリーDOI: 10.2210/pdb2v0c/pdb
• 関連するPDBエントリー: 1H3N 1OBC 1OBH 2BTE 2BYT
• 分子名称: AMINOACYL-TRNA SYNTHETASE, LEUCINE, [(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDRO-2-FURANYL]METHYL SULFAMATE, ... (7 entities in total)
• 機能のキーワード: ligase, nucleotide-binding, protein biosynthesis, clss i aminoacyl- trna synthetase, atp + l-leucine + trna (leu) gives amp + ppi + l-leucyl-trna(leu), aminoacyl-trna synthetase, zinc, atp-binding, metal-binding
• 由来する生物種: THERMUS THERMOPHILUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 102566.67

構造登録者

Rock, F.,Mao, W.,Yaremchuk, A.,Tukalo, M.,Crepin, T.,Zhou, H.,Zhang, Y.,Hernandez, V.,Akama, T.,Baker, S.,Plattner, J.,Shapiro, L.,Martinis, S.A.,Benkovic, S.J.,Cusack, S.,Alley, M.R.K. (登録日: 2007-05-14, 公開日: 2007-07-03, 最終更新日: 2023-12-13)

主引用文献

Rock, F.,Mao, W.,Yaremchuk, A.,Tukalo, M.,Crepin, T.,Zhou, H.,Zhang, Y.,Hernandez, V.,Akama, T.,Baker, S.,Plattner, J.,Shapiro, L.,Martinis, S.A.,Benkovic, S.J.,Cusack, S.,Alley, M.R.K.
An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site.
Science, 316:1759-, 2007

PubMed Abstract: Aminoacyl-transfer RNA (tRNA) synthetases, which catalyze the attachment of the correct amino acid to its corresponding tRNA during translation of the genetic code, are proven antimicrobial drug targets. We show that the broad-spectrum antifungal 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), in development for the treatment of onychomycosis, inhibits yeast cytoplasmic leucyl-tRNA synthetase by formation of a stable tRNA(Leu)-AN2690 adduct in the editing site of the enzyme. Adduct formation is mediated through the boron atom of AN2690 and the 2'- and 3'-oxygen atoms of tRNA's3'-terminal adenosine. The trapping of enzyme-bound tRNA(Leu) in the editing site prevents catalytic turnover, thus inhibiting synthesis of leucyl-tRNA(Leu) and consequentially blocking protein synthesis. This result establishes the editing site as a bona fide target for aminoacyl-tRNA synthetase inhibitors.

PubMed: 17588934
DOI: 10.1126/SCIENCE.1142189

実験手法

X-RAY DIFFRACTION (1.85 Å)