Aminoacyl-tRNA synthetases as therapeutic targets.,Nature Reviews Drug Discovery

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Aminoacyl-tRNA synthetases as therapeutic targets.
Nature Reviews Drug Discovery ( IF 122.7 ) Pub Date : 2019-08-01 , DOI: 10.1038/s41573-019-0026-3
Nam Hoon Kwon _{1,

2} , Paul L Fox ₃ , Sunghoon Kim _{1,

2}

Affiliation

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for protein synthesis with evolutionarily conserved enzymatic mechanisms. Despite their similarity across organisms, scientists have been able to generate effective anti-infective agents based on the structural differences in the catalytic clefts of ARSs from pathogens and humans. However, recent genomic, proteomic and functionomic advances have unveiled unexpected disease-associated mutations and altered expression, secretion and interactions in human ARSs, revealing hidden biological functions beyond their catalytic roles in protein synthesis. These studies have also brought to light their potential as a rich and unexplored source for new therapeutic targets and agents through multiple avenues, including direct targeting of the catalytic sites, controlling disease-associated protein-protein interactions and developing novel biologics from the secreted ARS proteins or their parts. This Review addresses the emerging biology and therapeutic applications of human ARSs in diseases including autoimmune and rare diseases, and cancer.

中文翻译：

氨酰基-tRNA合成作为治疗靶标。

氨酰基-tRNA合成酶（ARS）是蛋白质合成中必不可少的酶，具有进化上保守的酶促机制。尽管它们在生物体中具有相似性，但科学家已经能够根据病原体和人类产生的ARS催化裂隙中的结构差异产生有效的抗感染剂。然而，最近的基因组，蛋白质组和功能组学进展揭示了人类ARS中与疾病相关的意想不到的突变以及表达，分泌和相互作用的改变，揭示了蛋白质合成中催化作用以外的隐藏生物学功能。这些研究还通过多种途径（包括直接靶向催化部位，控制与疾病相关的蛋白质-蛋白质相互作用，并从分泌的ARS蛋白质或其部分中开发新的生物制剂。本综述探讨了人类ARS在包括自身免疫和罕见疾病以及癌症在内的疾病中新兴的生物学和治疗应用。

更新日期：2019-05-16

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