ArticleChemistry & biology2015
Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP Competitive Inhibitor.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 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
- Specific glycine-dependent enzyme motion determines the potency of conformation selective inhibitors of threonyl-tRNA synthetase.Communications biology · 2024Article
- Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.Communications biology · 2024Article
- Sequential magnesium binding facilitates lysyl-tRNA synthetase to recognize ATP.Biochemistry and biophysics reports · 2023Article
- Towards Novel 3-Aminopyrazinamide-Based Prolyl-tRNA Synthetase Inhibitors: In Silico Modelling, Thermal Shift Assay and Structural Studies.International journal of molecular sciences · 2021Article
- Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases.RSC chemical biology · 2021Review
- Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase.Nature communications · 2021Article
- Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.International journal of molecular sciences · 2021Review
- Intracellular CaInternational journal of molecular sciences · 2021Review
- Melatonin action in Plasmodium infection: Searching for molecules that modulate the asexual cycle as a strategy to impair the parasite cycle.Journal of pineal research · 2021Review
- Recent Development of Aminoacyl-tRNA Synthetase Inhibitors for Human Diseases: A Future Perspective.Biomolecules · 2020Review
- Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor.Nucleic acids research · 2020Article
- In silico assessment of natural products and approved drugs as potential inhibitory scaffolds targeting aminoacyl-tRNA synthetases from3 Biotech · 2020Article
- Two Forms of Tyrosyl-tRNA Synthetase fromSLAS discovery : advancing life sciences R & D · 2020Article
- Lysyl-tRNA Synthetase fromSLAS discovery : advancing life sciences R & D · 2020Article
- Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases.Cell death & disease · 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
- Aminoacyl-tRNA synthetases as therapeutic targets.Nature reviews. Drug discovery · 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
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6 authors at 1 institution in 2 countries.
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Abstract
Pharmaceutical inhibitors of aminoacyl-tRNA synthetases demand high species and family specificity. The antimalarial ATP-mimetic cladosporin selectively inhibits Plasmodium falciparum LysRS (PfLysRS). How the binding to a universal ATP site achieves the specificity is unknown. Here we report three crystal structures of cladosporin with human LysRS, PfLysRS, and a Pf-like human LysRS mutant. In all three structures, cladosporin occupies the class defining ATP-binding pocket, replacing the adenosine portion of ATP. Three residues holding the methyltetrahydropyran moiety of cladosporin are critical for the specificity of cladosporin against LysRS over other class II tRNA synthetase families. The species-exclusive inhibition of PfLysRS is linked to a structural divergence beyond the active site that mounts a lysine-specific stabilizing response to binding cladosporin. These analyses reveal that inherent divergence of tRNA synthetase structural assembly may allow for highly specific inhibition even through the otherwise universal substrate binding pocket and highlight the potential for structure-driven drug development.
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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.