Aminoacyl-tRNA synthetases have three important functions in the cell. They use ATP to activate the alpha carboxyl group, making the amino acid more reactive (Activation). This activation step adds the adenosine moiety as an “affinity tag” to the amino acid, increasing its binding affinity by ~1000-fold (Retention) This slows the release of a very reactive species and enables subsequent steps that enhance the fidelity of the final step. Finally, they catalyze transfer of the activated carboxyl group to the 3’ CCA terminus of tRNA (Acylation), completing the translation of the genetic code by the covalent linkage to the tRNA anticodon that is interpreted by the 30S ribosomal subunit in response to codons in mRNA. The approximate rate accelerations achieved by contemporary enzymes indicated are based on comparisons of kcat/KM values to the uncatalyzed rates, estimated from experimental rates of model reactions, as described in [38, 39].