3HXX

Crystal Structure of catalytic fragment of E. coli AlaRS in complex with AMPPCP

3HXX の概要

• エントリーDOI: 10.2210/pdb3hxx/pdb
• 関連するPDBエントリー: 3HXU 3HXV 3HXW 3HXY 3HXZ 3HY0 3HY1
• 分子名称: Alanyl-tRNA synthetase, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, ligase, protein biosynthesis, nucleotide-binding, amino acid-binding, atp-binding, metal-binding, zinc-finger
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P00957
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50502.18

構造登録者

Guo, M.,Yang, X.-L.,Schimmel, P. (登録日: 2009-06-22, 公開日: 2009-12-15, 最終更新日: 2024-02-21)

主引用文献

Guo, M.,Chong, Y.E.,Shapiro, R.,Beebe, K.,Yang, X.L.,Schimmel, P.
Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.
Nature, 462:808-812, 2009

PubMed Abstract: Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.

PubMed: 20010690
DOI: 10.1038/nature08612

実験手法

X-RAY DIFFRACTION (2.11 Å)