Putting amino acids onto tRNAs: The aminoacyl-tRNA synthetases as catalysts

Abstract

In this chapter we consider the catalytic approaches used by aminoacyl-tRNA synthetase (AARS) enzymes to synthesize aminoacyl-tRNA from cognate amino acid and tRNA. This ligase reaction proceeds through an activated aminoacyl-adenylate (aa-AMP). Common themes among AARSs include use of induced fit to drive catalysis and transition state stabilization by class-conserved sequence and structure motifs. Active site metal ions contribute to the amino acid activation step, while amino acid transfer to tRNA is generally a substrate-assisted concerted mechanism. A distinction between classes is the rate-limiting step for aminoacylation. We present some examples for each aspect of aminoacylation catalysis, including the experimental approaches developed to address questions of AARS chemistry.

Keywords: Aminoacyl-tRNA synthetase; Catalysis; Concerted; Divalent metals; Dynamics; Enzyme mechanisms; Induced fit; Nucleophile; Rate-limiting step; Substrate-assisted; Transition state; tRNA.