ArticleThe Journal of biological chemistry2009
The antimalarial drug quinine disrupts Tat2p-mediated tryptophan transport and causes tryptophan starvation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Cinchona-based liquid formulation exhibits antifungal activity through Tryptophan starvation and disruption of mitochondrial respiration in Rhizoctonia Solani.Scientific reports · 2025Article
- Cellular Responses and Targets in Food Spoilage Yeasts Exposed to Antifungal Prenylated Isoflavonoids.Microbiology spectrum · 2023Article
- Impaired amino acid uptake leads to global metabolic imbalance of Candida albicans biofilms.NPJ biofilms and microbiomes · 2022Article
- An Adjuvant-Based Approach Enables the Use of DominantmSphere · 2022Article
- New Insights into Quinine-DNA Binding Using Raman Spectroscopy and Molecular Dynamics Simulations.The journal of physical chemistry. B · 2018Article
- Acetaminophen reduces the protein levels of high affinity amino acid permeases and causes tryptophan depletion.Amino acids · 2018Article
- Heterologous Expression of a Novel Drug Transporter from the Malaria Parasite Alters Resistance to Quinoline Antimalarials.Scientific reports · 2018Article
- Novel Combinations of Agents Targeting Translation That Synergistically Inhibit Fungal Pathogens.Frontiers in microbiology · 2018Article
- Mitochondrial Ferredoxin Determines Vulnerability of Cells to Copper Excess.Cell chemical biology · 2017Article
- Oral quinine sulfate for the treatment of electrical storm and prevention of recurrent shocks in Brugada syndrome after failed cilostazol therapy.HeartRhythm case reports · 2017Article
- The Candidate Antimalarial Drug MMV665909 Causes Oxygen-Dependent mRNA Mistranslation and Synergizes with Quinoline-Derived Antimalarials.Antimicrobial agents and chemotherapy · 2017Article
- Novel, Synergistic Antifungal Combinations that Target Translation Fidelity.Scientific reports · 2015Article
- The antimalarial drug quinine interferes with serotonin biosynthesis and action.Scientific reports · 2014Article
- Cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine.Antimicrobial agents and chemotherapy · 2013Article
- Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species.Molecular biology of the cell · 2012Article
- Yeast toxicogenomics: genome-wide responses to chemical stresses with impact in environmental health, pharmacology, and biotechnology.Frontiers in genetics · 2012Article
- A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine.Molecular genetics and genomics : MGG · 2011Article
- Compound prioritization methods increase rates of chemical probe discovery in model organisms.Chemistry & biology · 2011Article
- Functional expression of parasite drug targets and their human orthologs in yeast.PLoS neglected tropical diseases · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quinine is a major drug of choice for the treatment of malaria. However, the primary mode of quinine action is unclear, and its efficacy is marred by adverse reactions among patients. To help address these issues, a genome-wide screen for quinine sensitivity was carried out using the yeast deletion strain collection. Quinine-sensitive mutants identified in the screen included several that were defective for tryptophan biosynthesis (trp strains). This sensitivity was confirmed in independent assays and was suppressible with exogenous Trp, suggesting that quinine caused Trp starvation. Accordingly, quinine was found to inhibit [(3)H]Trp uptake by cells, and the quinine sensitivity of a trp1Delta mutant could be rescued by overexpression of Trp permeases, encoded by TAT1 and TAT2. The site of quinine action was identified specifically as the high affinity Trp/Tyr permease, Tat2p, with which quinine associated in a Trp-suppressible manner. A resultant action also on Tyr levels was reflected by the Tyr-suppressible quinine hypersensitivity of an aro7Delta deletion strain, which is auxotrophic for Tyr (and Phe). The present genome-wide dataset provides an important resource for discovering modes of quinine toxicity. That potential was validated with our demonstration that Trp and Tyr uptake via Tat2p is a major target of cellular quinine toxicity. The results also suggest that dietary tryptophan supplements could help to avert the toxic effects of quinine.
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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.