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 ResearchConceptsSusceptibility 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
High-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
2015
Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening
Choi JY, Kumar V, Pachikara N, Garg A, Lawres L, Toh J, Voelker DR, Ben Mamoun C. Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. Molecular Microbiology 2015, 99: 999-1014. PMID: 26585333, PMCID: PMC4898484, DOI: 10.1111/mmi.13280.Peer-Reviewed Original ResearchConceptsClass of enzymesDevelopment of antimicrobialsYeast genesMembrane biogenesisEukaryotic pathogensProenzyme processingMammalian cellsPhosphatidylserine decarboxylasePSD activityPhospholipid biosynthesisParasite enzymeEssential functionsGenetic studiesMetabolic analysisAmino acidsDecarboxylase enzymePhosphatidylethanolamine synthesisPosition 40Inhibitor screeningEssential roleYeastEnzymePlasmodium falciparumSuitable targetNovel class