ArticleStructure (London, England : 1993)2022
High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development.
Article in Structure (London, England : 1993), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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5 citing papers in PubMed, 8 citations in OpenAlex.
- Functional and Biochemical Characterization of Spermidine Synthase CauSpe3 fromPathogens (Basel, Switzerland) · 2026Article
- Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi.Communications biology · 2024Article
- Coenzyme A biosynthesis: mechanisms of regulation, function and disease.Nature metabolism · 2024Review
- Article
- Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress.International journal of molecular sciences · 2022Article
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19 authors at 4 institutions in 1 country.
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Abstract
Fungal infections are the leading cause of mortality by eukaryotic pathogens, with an estimated 150 million severe life-threatening cases and 1.7 million deaths reported annually. The rapid emergence of multidrug-resistant fungal isolates highlights the urgent need for new drugs with new mechanisms of action. In fungi, pantothenate phosphorylation, catalyzed by PanK enzyme, is the first step in the utilization of pantothenic acid and coenzyme A biosynthesis. In all fungi sequenced so far, this enzyme is encoded by a single PanK gene. Here, we report the crystal structure of a fungal PanK alone as well as with high-affinity inhibitors from a single chemotype identified through a high-throughput chemical screen. Structural, biochemical, and functional analyses revealed mechanisms governing substrate and ligand binding, dimerization, and catalysis and helped identify new compounds that inhibit the growth of several Candida species. The data validate PanK as a promising target for antifungal drug development.
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