The Scripps Laboratories for tRNA Synthetase Research and the Department of Molecular Medicine, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 92037, La Jolla, CA, USA.
Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, China.
Nat Commun. 2017 Dec 22;8(1):2281. doi: 10.1038/s41467-017-02201-z.
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.
植物中存在数百种非蛋白氨基酸（npAA），原则上可以通过食物进入人体蛋白质合成。虽然氨酰-tRNA 合成酶（AARS）编辑提供了一种排斥 npAA 的机制，但有些与病理学有关。共晶结构表明，来源于植物的氮杂环丁烷-2-羧酸（Aze）是脯氨酸和丙氨酸的双重模拟物，可被人类脯氨酰-tRNA 合成酶和丙氨酰-tRNA 合成酶激活。然而，它作为脯氨酸插入蛋白质中，在体内产生毒性后果。因此，双重模拟通过逃避一个而不是两个 tRNA 合成酶编辑系统增加了翻译错误的可能性。
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