ArticleAntimicrobial agents and chemotherapy2009
Inhibition of inositol phosphorylceramide synthase by the cyclic peptide aureobasidin A.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Molecular insights into fungal inositol phosphorylceramide synthesis and its inhibition by antifungal aureobasidin A.Nature communications · 2026Article
- Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.Acta pharmaceutica Sinica. B · 2025Review
- Mechanisms of aureobasidin A inhibition and drug resistance in a fungal IPC synthase complex.Nature communications · 2025Article
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Antifungal activity of indolicidin-derived peptide In-58 againstFrontiers in medicine · 2024Article
- Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains ofJournal of fungi (Basel, Switzerland) · 2023Article
- Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Elevated levels of sphingolipid MIPC in the plasma membrane disrupt the coordination of cell growth with cell wall formation in fission yeast.PLoS genetics · 2023Article
- Beyond Ergosterol: Strategies for Combatting Antifungal Resistance inTetrahedron · 2023Article
- Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms.International journal of molecular sciences · 2022Review
- Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections.Frontiers in microbiology · 2022Review
- Sphingolipid Inhibitors as an Alternative to Treat Candidiasis Caused by Fluconazole-Resistant Strains.Pathogens (Basel, Switzerland) · 2021Article
- The Future of Antifungal Drug Therapy: Novel Compounds and Targets.Antimicrobial agents and chemotherapy · 2021Review
- Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of theACS infectious diseases · 2021Article
- Review
- Antifungal Drug Development: Targeting the Fungal Sphingolipid Pathway.Journal of fungi (Basel, Switzerland) · 2020Review
- Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723.BMC genomics · 2019Article
- The Yin and Yang of Current Antifungal Therapeutic Strategies: How Can We Harness Our Natural Defenses?Frontiers in pharmacology · 2019Review
- Sphingolipids activate the endoplasmic reticulum stress surveillance pathway.The Journal of cell biology · 2018Article
- Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis.Parasitology · 2018Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
By using a detergent-washed membrane preparation, the interaction of the fungal natural product inhibitor aureobasidin A (AbA) with inositol phosphorylceramide synthase (IPC synthase) was studied by kinetic analysis of wild-type and mutant enzyme-catalyzed reactions. AbA inhibited the wild-type enzyme from both Candida albicans and Saccharomyces cerevisiae in an irreversible, time-dependent manner, with apparent K(i) values of 183 and 234 pM, respectively. Three synthetic chemistry-derived AbA derivatives, PHA-533179, PHA-556655, and PHA-556656, had affinities 4 to 5 orders of magnitude lower and were reversible inhibitors that competed with the donor substrate phosphatidylinositol (PI). AbA was a reversible, apparently noncompetitive inhibitor, with a K(i) of 1.4 microM, of the IPC synthase from an AbA-resistant S. cerevisiae mutant. The K(m) values for both substrates (ceramide and PI) were similar when they interacted with the mutant and the wild-type enzymes. By contrast, the V(max) for the mutant enzyme was less than 10% of that for the wild-type enzyme. A comparison of the results obtained with AbA with those obtained with two other natural products inhibitors, rustmicin and khafrefungin, revealed that while rustmicin appeared to be a reversible, noncompetitive inhibitor of the wild-type enzyme, with a K(i) of 16.0 nM, khafrefungin had the kinetic properties of a time-dependent inhibitor and an apparent K(i) of 0.43 nM. An evaluation of the efficiencies of these compounds as inhibitors of the mutant enzyme revealed for both a drop in the apparent affinity for the enzyme of more than 2 orders of magnitude.
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Registered trials
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