ArticleACS infectious diseases2017
Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase.
Article in ACS infectious diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Inhibition of prolyl-tRNA synthetase and efflux pumps as a dual-targeting strategy against multidrug-resistant bacteria.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- PfATP2 is a flippase on the Plasmodium falciparum surface that is important for growth and influences parasite sensitivity to antiplasmodial compounds.PLoS pathogens · 2025Article
- Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease.Science translational medicine · 2025Article
- ATP mimetics targeting prolyl-tRNA synthetases as a new avenue for antimalarial drug development.iScience · 2024Article
- A pH Fingerprint Assay to Identify Inhibitors of Multiple Validated and Potential Antimalarial Drug Targets.ACS infectious diseases · 2024Article
- Article
- Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii.Scientific reports · 2023Article
- Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis.PLoS pathogens · 2023Article
- Transcriptome profile of halofuginone resistant and sensitive strains ofFrontiers in microbiology · 2023Article
- A G358S mutation in the Plasmodium falciparum NaNature communications · 2022Article
- Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance.Nature communications · 2022Article
- Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development.PLoS pathogens · 2022Article
- Repositioning and Characterization of 1-(Pyridin-4-yl)pyrrolidin-2-one Derivatives asACS infectious diseases · 2021Article
- SSnet: A Deep Learning Approach for Protein-Ligand Interaction Prediction.International journal of molecular sciences · 2021Article
- The Multifaceted Roles of Proline in Cell Behavior.Frontiers in cell and developmental biology · 2021Review
- Halofuginone Sensitizes Lung Cancer Organoids to CisplatinFrontiers in cell and developmental biology · 2021Article
- Naegleria fowleri: Protein structures to facilitate drug discovery for the deadly, pathogenic free-living amoeba.PloS one · 2021Article
- In silico assessment of natural products and approved drugs as potential inhibitory scaffolds targeting aminoacyl-tRNA synthetases from3 Biotech · 2020Article
- Pyrazolyl-Ureas as Interesting Scaffold in Medicinal Chemistry.Molecules (Basel, Switzerland) · 2020Review
- Identification of Selective Novel Hits againstInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
26 authors at 7 institutions in 4 countries.
Funding
Abstract
Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit PfProRS enzyme activity versus Homo sapiens (Hs) ProRS. X-ray crystallography structures were solved for apo, as well as substrate- and inhibitor-bound forms of PfProRS. We identified two new inhibitors of PfProRS that bind outside the active site. These two allosteric inhibitors showed >100 times specificity for PfProRS compared to HsProRS, demonstrating this class of compounds could overcome the toxicity related to HsProRS inhibition by halofuginone and its analogues. Initial medicinal chemistry was performed on one of the two compounds, guided by the cocrystallography of the compound with PfProRS, and the results can instruct future medicinal chemistry work to optimize these promising new leads for drug development against malaria.
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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.