5V59

Crystal structure of catalytic fragment of human AlaRS in complex with Aze-SA

5V59 の概要

• エントリーDOI: 10.2210/pdb5v59/pdb
• 関連するPDBエントリー: 5V58
• 分子名称: Alanine--tRNA ligase, cytoplasmic, 5'-O-{[(2S)-azetidine-2-carbonyl]sulfamoyl}adenosine (3 entities in total)
• 機能のキーワード: ligase, aminoacyl-trna synthetase, non-proteinogenic amino acid
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53743.60

構造登録者

Zhou, H.,Song, Y.,Schimmel, P. (登録日: 2017-03-13, 公開日: 2018-01-10, 最終更新日: 2023-10-04)

主引用文献

Song, Y.,Zhou, H.,Vo, M.N.,Shi, Y.,Nawaz, M.H.,Vargas-Rodriguez, O.,Diedrich, J.K.,Yates, J.R.,Kishi, S.,Musier-Forsyth, K.,Schimmel, P.
Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.
Nat Commun, 8:2281-2281, 2017

PubMed Abstract: Hundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle enter human protein synthesis through foods. While aminoacyl-tRNA synthetase (AARS) editing potentially provides a mechanism to reject np AAs, some have pathological associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid (Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not both tRNA synthetase editing systems.

PubMed: 29273753
DOI: 10.1038/s41467-017-02201-z

実験手法

X-RAY DIFFRACTION (2.03 Å)