ArticlePLoS neglected tropical diseases2016
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- Aminoisothiazolamides, a new class of potent inhibitors of lysyl-tRNA synthetase.Pest management science · 2025Article
- Genomic analysis of single nucleotide polymorphisms in malaria parasite drug targets.Parasites & vectors · 2022Article
- Lyme disease transmission by severely impaired ticks.Open biology · 2022Article
- Drug targeting of aminoacyl-tRNA synthetases in Anopheles species and Aedes aegypti that cause malaria and dengue.Parasites & vectors · 2021Article
- Bicyclic azetidines kill the diarrheal pathogenScience translational medicine · 2020Article
- Conformational heterogeneity in apo and drug-bound structures of Toxoplasma gondii prolyl-tRNA synthetase.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Aminoacyl tRNA synthetases as potential drug targets of the Panthera pathogen Babesia.Parasites & vectors · 2019Article
- Article
- Genetic manipulation of Leishmania donovani threonyl tRNA synthetase facilitates its exploration as a potential therapeutic target.PLoS neglected tropical diseases · 2018Article
- Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms.Scientific reports · 2017Article
- Genetic Validation ofmSphereArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections are typified by limited clinical treatment options and threat of drug resistance. Aminoacyl-tRNA synthetases (aaRSs) are vital enzymes that decode genetic information and enable protein translation. The specific inhibition of pathogen aaRSs bores well for development of next generation anti-parasitics. Here, we have identified and annotated aaRSs and accessory proteins from Loa loa (nematode) and Schistosoma mansoni (flatworm) to provide a glimpse of these protein translation enzymes within these parasites. Using purified parasitic lysyl-tRNA synthetases (KRSs), we developed series of assays that address KRS enzymatic activity, oligomeric states, crystal structure and inhibition profiles. We show that L. loa and S. mansoni KRSs are potently inhibited by the fungal metabolite cladosporin. Our co-crystal structure of Loa loa KRS-cladosporin complex reveals key interacting residues and provides a platform for structure-based drug development. This work hence provides a new direction for both novel target discovery and inhibitor development against eukaryotic pathogens that include L. loa and S. mansoni.
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