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 ResearchMeSH KeywordsHomeostasisHumansIronMitochondriaOxidative StressPantothenate Kinase-Associated NeurodegenerationPantothenic AcidPhosphotransferases (Alcohol Group Acceptor)Saccharomyces cerevisiaeConceptsPantothenate 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 mechanismCatalysisBiosynthesisKinaseRedesigning therapies for pantothenate kinase–associated neurodegeneration
Munshi MI, Yao SJ, Mamoun C. Redesigning therapies for pantothenate kinase–associated neurodegeneration. Journal Of Biological Chemistry 2022, 298: 101577. PMID: 35041826, PMCID: PMC8861153, DOI: 10.1016/j.jbc.2022.101577.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoenzyme AHumansMutationNeurodegenerative DiseasesPantothenate Kinase-Associated NeurodegenerationPhosphotransferases (Alcohol Group Acceptor)ConceptsPantothenate kinase-associated neurodegenerationCellular metabolic processesMore common diseasesMetabolic processesPhysiological importancePANK2 genePantothenate kinaseCoenzyme ACoenzyme A.Rare genetic disorderCommon neurodegenerative diseaseNeurodegenerative diseasesGenetic disordersNeurodegenerationNew avenuesBiosynthesisKinaseGenesNew lightFuture investigationsCofactorMutationsCommon diseaseEnzymeAlzheimer's disease