Wolbachia leucyl-tRNA synthetase

Wolbachia leucyl-tRNA synthetase is a bacterial aminoacyl-tRNA synthetase distinct from human and other eukaryotic LeuRS, responsible for ligating leucine to tRNA(Leu) as a key step in protein translation[1][5][6]. Structural studies reveal that this enzyme in Wolbachia has unique features in the drug-binding pocket—such as rare cysteines—that provide selectivity for small-molecule inhibition[1]. This enzyme is essential for the survival of Wolbachia and, by extension, for the lifecycle of filarial parasites responsible for major infectious diseases. Drugs targeting Wolbachia LeuRS exploit its unique structure to selectively inhibit its activity, thereby blocking parasite development and transmission without affecting host protein synthesis[5][1][6]. Benzoxaborole-class inhibitors that form stable adducts at the enzyme’s editing domain are a leading strategy for eliminating Wolbachia and treating filariasis.

Other names

Wolbachia LeuRSLeucine--tRNA ligase (bacterial context)leuS (gene name in genome annotations)

Enzyme inhibition (benzoxaboroles and boron-based compounds inhibit leucyl-tRNA synthetase by binding the editing site and forming adducts with tRNA, blocking aminoacylation and editing activity, thereby arresting protein synthesis[1][5][6])