aaRS

Aminoacyl-tRNA synthetases (aaRS) are enzymes that charge transfer RNAs (tRNAs) with their cognate amino acids, forming aminoacyl-tRNAs that ferry amino acids to the ribosome during protein synthesis. Each aaRS recognizes a specific amino acid and its corresponding tRNA(s), ensuring the correct translation of the genetic code.

The catalytic cycle is two-step. First, the amino acid is activated by ATP to form an aminoacyl-adenylate (aminoacyl-AMP) and pyrophosphate. In the second step, the activated amino acid is transferred to the 3' end of the tRNA, producing aminoacyl-tRNA and AMP. The tRNA identity elements and the enzyme’s active site cooperate to ensure proper pairing of amino acid and tRNA.

aaRSs are divided into two structural classes, I and II, based on conserved motifs and chemistry. Class I enzymes typically attach the amino acid to the 2'-OH of the terminal adenosine and often contain an editing domain that can proofread misacylated tRNAs; class II enzymes generally charge at the 3'-OH and exhibit different architectural features. Several aaRSs possess intrinsic editing activities to hydrolyze incorrect aminoacyl-tRNAs and thus reduce translational errors (examples include IleRS, LeuRS, ValRS, and ProRS).

Distribution and importance: aaRSs are essential in all domains of life and also function in organelles such as mitochondria and chloroplasts, where organelle-targeted versions may be encoded in the nucleus. Because fidelity of protein synthesis depends on proper aminoacylation, aaRSs are central to cellular biology and are studied for antibiotic targeting and for enabling the incorporation of noncanonical amino acids into proteins.