Leucine—tRNA ligase

Leucine—tRNA ligase, also known as leucyl-tRNA synthetase, is an enzyme that belongs to the class of aminoacyl-tRNA synthetases (AARSs). This enzyme plays a crucial role in the process of protein synthesis by attaching the amino acid leucine to its corresponding transfer RNA (tRNA), a step critical for the translation of genetic information into functional proteins. The enzyme is encoded by the LARS gene in humans.

Function

Leucine—tRNA ligase catalyzes the ATP-dependent attachment of leucine to its cognate tRNA, producing leucyl-tRNA and AMP as products. This reaction occurs in two steps: first, the enzyme catalyzes the activation of leucine by ATP to form leucyl-AMP and pyrophosphate (PPi); second, it transfers the activated leucine to the 3' end of tRNA^Leu. This process is essential for the accurate translation of the mRNA code into a polypeptide chain during protein biosynthesis.

Structure

The structure of leucine—tRNA ligase is characterized by several domains: the catalytic domain, which is responsible for the enzyme's aminoacylation activity; the editing domain, which ensures the accuracy of tRNA aminoacylation by hydrolyzing incorrectly charged tRNA; and the anticodon-binding domain, which recognizes the anticodon loop of tRNA^Leu. The enzyme exists in both cytoplasmic and mitochondrial forms, encoded by separate genes, reflecting the dual role of leucine in protein synthesis in both cellular compartments.

Clinical Significance

Mutations in the LARS gene have been associated with various human diseases. Defects in leucine—tRNA ligase can lead to disorders of amino acid metabolism and have been linked to conditions such as neuropathy and autoimmune diseases. The enzyme's role in protein synthesis also makes it a potential target for the development of antibacterial and antiviral agents, as well as cancer therapeutics, by inhibiting protein synthesis in pathogens or cancer cells.

Evolution

Leucine—tRNA ligase is part of the aminoacyl-tRNA synthetase family, which is believed to be among the first proteins to have evolved, given their central role in protein synthesis. The enzyme is highly conserved across all domains of life, highlighting its fundamental importance in cellular biology.

See Also

• Aminoacyl-tRNA synthetase
• Protein synthesis
• Leucine
• Transfer RNA