Aminoacyl-tRNA synthetase:transfer RNA (aaRS:tRNA) systems became recently essential
targets in molecular medicine, because perturbed recognition of cognate tRNAs by aaRSs and poor
precision in tRNA aminoacylation do not guarantee accurate protein biosynthesis, thus leading to diseases.
Sets of identity determinants situated at particular zones of tRNA are responsible for functional
accuracy. Recent work in X-ray crystallography has revealed various snapshots of aaRS:ligand complexes
which represent the stages required for aminoacylation. Here we focus on a small group of
class I aaRSs conserved in evolution, the ArgRSs, GluRSs, GlnRSs, and atypical LysRSs found
mostly in Archaea and in a few Bacteria, that catalyze amino acid activation only in the presence of their cognate tRNAs.
Structural and functional features of these aaRSs, ranked in subclass Ib, together with their peculiar mode of tRNA recognition
and identity expression are reviewed and compared. Strategies to inhibit class Ib aaRS:tRNA aminoacylation systems,
their dysfunction leading to human diseases, and the implications for pharmacology are outlined.
Keywords: Aminoacylation, tRNA, Aminoacyl-tRNA synthetase and diseases, Aminoacyl-tRNA synthetase as drug target,
Protein-biomolecule interactions, tRNA, tRNA identity determinants.
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