ArticleMolecular microbiology2016
Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening.
Article in Molecular microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- DVL, a Lectin fromAntibiotics (Basel, Switzerland) · 2025Article
- Biochemistry and Diseases Related to the Interconversion of Phosphatidylcholine, Phosphatidylethanolamine, and Phosphatidylserine.International journal of molecular sciences · 2024Review
- WIPI4 loss linked to ferroptosis.Nature cell biology · 2024Article
- Loss of WIPI4 in neurodegeneration causes autophagy-independent ferroptosis.Nature cell biology · 2024Article
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
- Single-cell quantitative bioimaging ofmSphere · 2023Article
- Metabolic Network Models of themSystems · 2023Article
- SMAC/Diablo controls proliferation of cancer cells by regulating phosphatidylethanolamine synthesis.Molecular oncology · 2021Article
- Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.PLoS neglected tropical diseases · 2021Article
- Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis.Scientific reports · 2021Article
- Review
- An improved and highly selective fluorescence assay for measuring phosphatidylserine decarboxylase activity.The Journal of biological chemistry · 2020Article
- High-throughput screening for phosphatidylserine decarboxylase inhibitors using a distyrylbenzene-bis-aldehyde (DSB-3)-based fluorescence assay.The Journal of biological chemistry · 2019Article
- The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.Cell stem cell · 2019Article
- Tafazzin modulates cellular phospholipid composition to regulate AML stemness.Molecular & cellular oncology · 2019Article
- Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood.The Journal of biological chemistry · 2018Review
- PS, It's Complicated: The Roles of Phosphatidylserine and Phosphatidylethanolamine in the Pathogenesis of Candida albicans and Other Microbial Pathogens.Journal of fungi (Basel, Switzerland) · 2018Review
- A novel fluorescence assay for measuring phosphatidylserine decarboxylase catalysis.The Journal of biological chemistry · 2018Article
- Article
- The Candidate Antimalarial Drug MMV665909 Causes Oxygen-Dependent mRNA Mistranslation and Synergizes with Quinoline-Derived Antimalarials.Antimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Phospholipid biosynthesis is critical for the development, differentiation and pathogenesis of several eukaryotic pathogens. Genetic studies have validated the pathway for phosphatidylethanolamine synthesis from phosphatidylserine catalyzed by phosphatidylserine decarboxylase enzymes (PSD) as a suitable target for development of antimicrobials; however no inhibitors of this class of enzymes have been discovered. We show that the Plasmodium falciparum PSD can restore the essential function of the yeast gene in strains requiring PSD for growth. Genetic, biochemical and metabolic analyses demonstrate that amino acids between positions 40 and 70 of the parasite enzyme are critical for proenzyme processing and decarboxylase activity. We used the essential role of Plasmodium PSD in yeast as a tool for screening a library of anti-malarials. One of these compounds is 7-chloro-N-(4-ethoxyphenyl)-4-quinolinamine, an inhibitor with potent activity against P. falciparum, and low toxicity toward mammalian cells. We synthesized an analog of this compound and showed that it inhibits PfPSD activity and eliminates Plasmodium yoelii infection in mice. These results highlight the importance of 4-quinolinamines as a novel class of drugs targeting membrane biogenesis via inhibition of PSD activity.
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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.