ArticleJournal of structural and functional genomics2014
Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.
Article in Journal of structural and functional genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 75 citations in OpenAlex.
- In Vivo Efficacy and Biochemical Target Engagement of a Chromene-Based Inhibitor of Trypanosoma cruzi Lysyl-tRNA Synthetase.Journal of medicinal chemistry · 2026Article
- Aminoisothiazolamides, a new class of potent inhibitors of lysyl-tRNA synthetase.Pest management science · 2025Article
- ATP mimetics targeting prolyl-tRNA synthetases as a new avenue for antimalarial drug development.iScience · 2024Article
- Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.Communications biology · 2024Article
- Article
- Toolkit of Approaches To Support Target-Focused Drug Discovery forACS infectious diseases · 2022Article
- Genomic analysis of single nucleotide polymorphisms in malaria parasite drug targets.Parasites & vectors · 2022Article
- Structural analyses of the malaria parasite aminoacyl-tRNA synthetases provide new avenues for antimalarial drug discovery.Protein science : a publication of the Protein Society · 2021Review
- Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.International journal of molecular sciences · 2021Review
- Structural basis of malaria parasite phenylalanine tRNA-synthetase inhibition by bicyclic azetidines.Nature communications · 2021Article
- The biological process of lysine-tRNA charging is therapeutically targetable in liver cancer.Liver international : official journal of the International Association for the Study of the Liver · 2021Article
- Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor.Nucleic acids research · 2020Article
- Experimental and Computational Investigations of the Reactions between α,β-Unsaturated Lactones and 1,3-Dienes by Cooperative Lewis Acid/Brønsted Acid Catalysis.Angewandte Chemie (International ed. in English) · 2020Article
- Profiles of Kelch mutations in Plasmodium falciparum across South Asia and their implications for tracking drug resistance.International journal for parasitology. Drugs and drug resistance · 2019Review
- 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
- Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics.The Journal of biological chemistry · 2019Review
- Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study.Malaria journal · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.