Fundamentals of Molecular Biology. Part 2: Molecular Genetic Mechanisms - A. N. Ogodzurtsov 2011

The Role of RNA in Translation
Amino Acid Activation by Aminoacyl-tRNA Synthetase

In fact, the recognition of the codon (or codons) specifying a given amino acid by a specific tRNA is the Second Stage in decoding Genetic information. The first step—attaching the appropriate amino acid to the tRNA—is catalyzed by a specialized enzyme called aminoacyl-tRNA synthetase. Each of the 20 different synthetases recognizes a single Amino Acid and all compatible (cognate) tRNAs.

Cognate tRNAs that possess different primary structures but identical tertiary structures and accept the same amino acid are referred to as isoaccepting tRNAs.

Aminoacyl-tRNA synthetase attaches The amino acid to the free 2' or 3' hydroxyl group of the adenosine pentose at the 3'-end of the tRNA molecule via an ATP-dependent reaction.

In this reaction (Figure 35), the amino acid is linked to the tRNA by a high-energy bond, which is why it is said to be activated. The energy of this bond is subsequently utilized to form the peptide bond linking adjacent Amino Acids in the growing polypeptide chain.

The equilibrium of the aminoacylation reaction is driven toward amino acid activation due to the Hydrolysis of the high-energy phosphoanhydride bond in the released pyrophosphate, yielding orthophosphate. This reaction is catalyzed by the enzyme pyrophosphatase, which thus plays a vital role in energetically driving the aminoacylation process in the forward direction.

Because Amino acids are structurally similar, aminoacyl-tRNA synthetase occasionally makes mistakes. However, these errors are corrected by the synthetase itself, as it features a specialized error-correction mechanism commonly referred to in literature as proofreading.

The "correctly" aminoacylated tRNA leaves the synthetase, whereas the "incorrectly" acylated one remains bound to the enzyme's Active Site, which catalyzes the removal of the "wrong" amino acid from the tRNA.

This mechanism ensures the accurate delivery of required amino acids to the site of Protein Synthesis. As a result, Translation in E. coli yields only one error per 50,000 codons, highlighting the remarkable efficiency of the aminoacyl-tRNA synthetase proofreading mechanism.