2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2014
Identification of Inhibitors of Inositol 5‑Phosphatases through Multiple Screening Strategies
Pirruccello M, Nandez R, Idevall-Hagren O, Alcazar-Roman A, Abriola L, Berwick SA, Lucast L, Morel D, De Camilli P. Identification of Inhibitors of Inositol 5‑Phosphatases through Multiple Screening Strategies. ACS Chemical Biology 2014, 9: 1359-1368. PMID: 24742366, PMCID: PMC4076014, DOI: 10.1021/cb500161z.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDermisElectrophoretic Mobility Shift AssayEnzyme InhibitorsFibroblastsFluorescence PolarizationHigh-Throughput Screening AssaysHumansInositol Polyphosphate 5-PhosphatasesMolecular StructurePhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesRosaniline DyesSignal TransductionSmall Molecule LibrariesThiadiazolesTriazolesConceptsPhosphoinositide-metabolizing enzymesGrowth factor signalingSmall molecule modulatorsIdentification of inhibitorsFamily of enzymesMembrane traffickingActin nucleationCytoskeletal dynamicsCell cortexPhosphoinositide levelsCatalytic domainFactor signalingMolecule modulatorsHigh-throughput screeningLiving cellsSpecific inhibitorActivity assaysMembrane phospholipidsDirect interactionCell proliferationChemical scaffoldsPowerful research toolPotential therapeutic applicationsOCRLPhosphoinositide