Isoleucine–tRNA ligase (IleRS)

Isoleucine–tRNA ligase (IleRS) is an essential enzyme that catalyzes the ATP-dependent attachment of isoleucine to its specific transfer RNA (tRNAIle) in a two-step reaction: activation of isoleucine to form isoleucyl-AMP, followed by transfer of isoleucine to tRNA. This process is fundamental for the fidelity of protein biosynthesis, ensuring that only isoleucine is incorporated where specified by the genetic code. IleRS has unique structural features, including distinct domains for tRNA recognition and post-transfer editing, which correct errors by removing incorrectly attached amino acids such as valine. The enzyme is highly conserved and present in bacteria, mitochondria, and the cytoplasm of eukaryotes, making it a validated antibacterial drug target, though careful molecular selectivity is required to avoid human toxicity. Inhibitors of aminoacyl-tRNA synthetases (like mupirocin for the related leucyl-tRNA synthetase) act by blocking protein synthesis, leading to cell growth arrest or death, a mechanism exploited for bacterial infections.

Other names

Isoleucyl-tRNA synthetaseIsoleucyl-transfer ribonucleate synthetaseIsoleucyl-transfer RNA synthetaseIsoleucine-transfer RNA ligaseIsoleucine-tRNA synthetaseIsoleucine translaseL-isoleucine:tRNAIle ligase (AMP-forming)

Enzyme inhibition