4TVA

Universal Pathway for Post-Transfer Editing Reactions: Insight from Crystal structure of TthPheRS with Puromycine

4TVA の概要

• エントリーDOI: 10.2210/pdb4tva/pdb
• 関連するPDBエントリー: 3HFZ
• 分子名称: Phenylalanine--tRNA ligase alpha subunit, Phenylalanine--tRNA ligase beta subunit, PHENYLALANINE, ... (5 entities in total)
• 機能のキーワード: puromycine, editing, trna, phers, ligase-antibiotic complex, ligase/antibiotic
• 由来する生物種: Thermus thermophilus; 詳細
• 細胞内の位置: Cytoplasm: P27001 P27002
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 126666.55

構造登録者

Safro, M.,Klipcan, L.,Tworowski, D.,Peretz, M. (登録日: 2014-06-26, 公開日: 2015-03-18, 最終更新日: 2023-09-27)

主引用文献

Tworowski, D.,Klipcan, L.,Peretz, M.,Moor, N.,Safro, M.G.
Universal pathway for posttransfer editing reactions: Insights from the crystal structure of TtPheRS with puromycin.
Proc.Natl.Acad.Sci.USA, 112:3967-3972, 2015

PubMed Abstract: At the amino acid binding and recognition step, phenylalanyl-tRNA synthetase (PheRS) faces the challenge of discrimination between cognate phenylalanine and closely similar noncognate tyrosine. Resampling of Tyr-tRNA(Phe) to PheRS increasing the number of correctly charged tRNA molecules has recently been revealed. Thus, the very same editing site of PheRS promotes hydrolysis of misacylated tRNA species, associated both with cis- and trans-editing pathways. Here we report the crystal structure of Thermus thermophilus PheRS (TtPheRS) at 2.6 Å resolution, in complex with phenylalanine and antibiotic puromycin mimicking the A76 of tRNA acylated with tyrosine. Starting from the complex structure and using a hybrid quantum mechanics/molecular mechanics approach, we investigate the pathways of editing reaction catalyzed by TtPheRS. We show that both 2' and 3' isomeric esters undergo mutual transformation via the cyclic intermediate orthoester, and the editing site can readily accommodate a model of Tyr-tRNA(Phe) where deacylation occurs from either the 2'- or 3'-OH. The suggested pathway of the hydrolytic reaction at the editing site of PheRS is of sufficient generality to warrant comparison with other class I and class II aminoacyl-tRNA synthetases.

PubMed: 25775602
DOI: 10.1073/pnas.1414852112

実験手法

X-RAY DIFFRACTION (2.597 Å)