Helicobacter pylori isoleucyl-tRNA synthetase (HpIleRS)

Helicobacter pylori isoleucyl-tRNA synthetase (IleRS) is an essential enzyme that catalyzes the attachment of the amino acid isoleucine to its cognate tRNA, a fundamental step in bacterial protein synthesis [1, 13]. As a member of the Class I aminoacyl-tRNA synthetases, it ensures the fidelity of translation by accurately pairing isoleucine with tRNA(Ile) through a two-step reaction involving an isoleucyl-adenylate intermediate [1, 13]. Because IleRS is indispensable for the survival of H. pylori and exhibits significant structural divergence from its human counterparts, it serves as a high-priority target for the development of novel antimicrobial agents [1, 6]. H. pylori is a major global pathogen linked to chronic gastritis, peptic ulcers, and gastric malignancies, and the rising prevalence of multidrug-resistant strains necessitates the exploration of targets like IleRS [1, 11]. Inhibitors such as mupirocin act by mimicking the isoleucyl-adenylate intermediate, thereby blocking the enzyme's active site and halting the production of essential proteins [1, 13]. Recent structural studies have provided a basis for the rational design of more selective and potent inhibitors to combat persistent infections [1].

Other names

Isoleucine-tRNA ligaseIsoleucine-tRNA synthetaseIleSIsoleucyl-tRNA ligaseHpIleRS

Inhibits protein synthesis by competitively binding to the isoleucyl-adenylate binding site of the enzyme, preventing the formation of isoleucyl-tRNA [1, 13].