A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding
Shillingford S, Zhang L, Surovtseva Y, Dorry S, Lolis E, Bennett AM. A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding. Journal Of Biological Chemistry 2022, 298: 102617. PMID: 36272649, PMCID: PMC9676401, DOI: 10.1016/j.jbc.2022.102617.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK bindingRegulatory mechanismsAllosteric siteMKP family membersNovel allosteric siteSmall molecule targetingMAPK/JNKAdditional regulatory mechanismsPhosphatase functionPhosphatase domainP38 MAPK/JNKProtein kinaseMKP7Site mutantsMAPK signalingAllosteric pocketMolecule targetingMAPK dephosphorylationMutantsNovel siteJNKCatalytic siteDephosphorylationDefining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors
Gannam Z, Jamali H, Kweon OS, Herrington J, Shillingford SR, Papini C, Gentzel E, Lolis E, Bennett AM, Ellman JA, Anderson KS. Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors. European Journal Of Medicinal Chemistry 2022, 243: 114712. PMID: 36116232, PMCID: PMC9830533, DOI: 10.1016/j.ejmech.2022.114712.Peer-Reviewed Original ResearchMeSH KeywordsStructure-Activity RelationshipConceptsStress-responsive MAPKsEnzyme-inhibitor complexDystrophic muscle diseasePhosphatase 5Muscle diseaseAllosteric inhibitorsNumber of diseasesNovel classProtein kinase phosphatase 5Structure-activity relationshipsPotential therapeutic targetMKP5X-ray crystal structureTherapeutic targetPotential therapeuticsInhibitorsLead compoundsInhibitionProper positioningMAPKCrystal structureMitogenTyr435Derivative compoundsInteraction