Leucine–tRNA ligase (LARS (human cytoplasmic form); LeuRS)

Leucine–tRNA ligase (LeuRS or LARS) is a class I aminoacyl-tRNA synthetase enzyme that catalyzes the ATP-dependent attachment of L-leucine to its cognate tRNA^Leu^ in a two-step reaction involving leucyl-adenylate formation and tRNA charging, ensuring accurate protein translation. It features a complex modular structure with a Rossmann-fold aminoacylation domain, anticodon-binding domain, editing domain (CP1) for hydrolyzing mischarged amino acids like norvaline or homocysteine, and a vertebrate C-terminal (VC) domain that binds tRNA and interacts with RagD to activate mTORC1 signaling. In humans, the cytoplasmic form (encoded by LARS1) assembles into a multisynthetase complex, linking translation to cellular metabolism. Bacterial orthologs like E. coli leuS share core functions but differ in editing domain insertion. While essential for cellular viability, human LeuRS has emerging non-canonical roles in nutrient sensing, positioning it as a potential therapeutic target in cancer where mTORC1 dysregulation drives proliferation, though no drugs are approved and inhibition risks translation disruption.

Other names

leucyl-tRNA synthetasecytosolic leucyl-tRNA synthetaseLARS1 (human)leuS (E. coli)

No approved drugs; research focuses on inhibition of aminoacylation or editing domains