3PD2

Crystal structure of the editing domain of threonyl-tRNA synthetase from Pyrococcus abyssi in complex with seryl-3'-aminoadenosine

3PD2 の概要

• エントリーDOI: 10.2210/pdb3pd2/pdb
• 関連するPDBエントリー: 1y2q 2hl0 2hl1 2hl2 3PD3 3PD4 3PD5
• 分子名称: Threonyl-tRNA synthetase, SERINE-3'-AMINOADENOSINE (3 entities in total)
• 機能のキーワード: alpha/beta fold, deacylase, editing, aminoacyl-trna synthetase, translation, ligase
• 由来する生物種: Pyrococcus abyssi
• 細胞内の位置: Cytoplasm (By similarity): Q9UZ14
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34183.29

構造登録者

Hussain, T.,Kamarthapu, V.,Kruparani, S.P.,Sankaranarayanan, R. (登録日: 2010-10-22, 公開日: 2010-12-08, 最終更新日: 2023-11-01)

主引用文献

Hussain, T.,Kamarthapu, V.,Kruparani, S.P.,Deshmukh, M.V.,Sankaranarayanan, R.
Mechanistic insights into cognate substrate discrimination during proofreading in translation
Proc.Natl.Acad.Sci.USA, 107:22117-22121, 2010

PubMed Abstract: Editing/proofreading by aminoacyl-tRNA synthetases is an important quality control step in the accurate translation of the genetic code that removes noncognate amino acids attached to tRNA. Defects in the process of editing result in disease conditions including neurodegeneration. While proofreading, the cognate amino acids larger by a methyl group are generally thought to be sterically rejected by the editing modules as envisaged by the "Double-Sieve Model." Strikingly using solution based direct binding studies, NMR-heteronuclear single quantum coherence (HSQC) and isothermal titration calorimetry experiments, with an editing domain of threonyl-tRNA synthetase, we show that the cognate substrate can gain access and bind to the editing pocket. High-resolution crystal structural analyses reveal that functional positioning of substrates rather than steric exclusion is the key for the mechanism of discrimination. A strategically positioned "catalytic water" molecule is excluded to avoid hydrolysis of the cognate substrate using a "RNA mediated substrate-assisted catalysis mechanism" at the editing site. The mechanistic proof of the critical role of RNA in proofreading activity is a completely unique solution to the problem of cognate-noncognate selection mechanism.

PubMed: 21098258
DOI: 10.1073/pnas.1014299107

実験手法

X-RAY DIFFRACTION (1.86 Å)