2024
Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi
Choi J, Gihaz S, Munshi M, Singh P, Vydyam P, Hamel P, Adams E, Sun X, Khalimonchuk O, Fuller K, Ben Mamoun C. Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi. Communications Biology 2024, 7: 894. PMID: 39043829, PMCID: PMC11266677, DOI: 10.1038/s42003-024-06595-7.Peer-Reviewed Original ResearchMeSH KeywordsAntifungal AgentsDrug Resistance, FungalInactivation, MetabolicMitochondriaPantothenic AcidSaccharomyces cerevisiaeVacuolesConceptsSusceptibility of fungiRegulation of genesMetabolism of fatty acidsVacuolar morphologySaccharomyces cerevisiaeAcetyl-CoAEukaryotic pathogensGenetic evidenceGenetic regulationCellular processesAntifungal drugsCo-enzyme ADrug detoxificationAntifungal therapyDrug-resistant strainsFungal infectionsMitochondrial functionFungiAmino acidsAR-12Vitamin B5Synthase activityPathwayExcellent targetGlobal health threat
2022
Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress
Ceccatelli Berti C, Gihaz S, Figuccia S, Choi J, Pal A, Goffrini P, Ben Mamoun C. Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress. International Journal Of Molecular Sciences 2022, 24: 435. PMID: 36613877, PMCID: PMC9820505, DOI: 10.3390/ijms24010435.Peer-Reviewed Original ResearchConceptsPantothenate Kinase-Associated NeurodegenerationFunctional conservationMitochondrial transit peptidePantothenate kinaseNormal cellular activitiesUse of yeastOverexpression of humanTransit peptideConserved functionYeast mutantsModel organismsPanK activityCellular functionsOxidative stressCellular conditionsMitochondrial homeostasisCellular cofactorsDefective growthKinase isoformsCellular activitiesMetabolic pathwaysYeastGenesMitochondrial dysfunctionBiochemical propertiesHigh-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development
Gihaz S, Gareiss P, Choi JY, Renard I, Pal AC, Surovsteva Y, Chiu JE, Thekkiniath J, Plummer M, Hungerford W, Montgomery ML, Hosford A, Adams EM, Lightfoot JD, Fox D, Ojo KK, Staker BL, Fuller K, Ben Mamoun C. High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development. Structure 2022, 30: 1494-1507.e6. PMID: 36167065, PMCID: PMC10042587, DOI: 10.1016/j.str.2022.09.001.Peer-Reviewed Original ResearchConceptsCrystal structureHigh-throughput chemical screenHigh-resolution crystal structuresAntifungal drug developmentHigh-affinity inhibitorsEukaryotic pathogensChemical screenNew compoundsSingle chemotypeFunctional analysisLigand bindingAntifungal developmentPantothenate phosphorylationFungal isolatesPantothenate kinaseNew targetsFungiPanKPromising targetEnzymeDrug developmentNew mechanismCatalysisBiosynthesisKinase