Isoleucine-tRNA ligase (IleRS)

Isoleucine-tRNA ligase is an essential aminoacyl-tRNA synthetase enzyme found in bacteria. It catalyzes the specific attachment of L-isoleucine to its corresponding tRNA (tRNA^Ile), a critical step in ensuring fidelity during translation and protein synthesis. This process involves two distinct steps: activation of isoleucine by ATP to form isoleucyl-AMP, followed by its transfer to tRNA—resulting in isoleucyl-tRNA and AMP. The enzyme also serves as a quality control checkpoint, employing both pre- and post-transfer editing mechanisms to prevent misacylation with similar amino acids, such as valine. Isoleucine-tRNA ligase is a well-characterized drug target, notably inhibited by mupirocin, which is used clinically against Gram-positive pathogens. Bacterial resistance can arise due to gene duplication and sequence variation (ileS1/ileS2), necessitating ongoing study for therapeutic efficacy. The enzyme plays central roles in bacterial growth and is indispensable for cell viability.

Other names

Isoleucyl-tRNA synthetaseIsoleucyl-transfer RNA synthetaseIsoleucyl-tRNA ligaseIsoleucine-tRNA synthetaseIsoleucine translaseL-isoleucine:tRNAIle ligase

Inhibition of aminoacylation: Mupirocin and related antibiotics bind to the enzyme, preventing the attachment of isoleucine to tRNA and thus halting protein synthesis