Aminoacyl-tRNA synthetases as therapeutic targets

Nam Hoon Kwon, Paul L. Fox, Sunghoon Kim

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)629-650
Number of pages22
JournalNature Reviews Drug Discovery
Volume18
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

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