Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention
Krimmer S, Bertoletti N, Suzuki Y, Katic L, Mohanty J, Shu S, Lee S, Lax I, Mi W, Schlessinger J. Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300054120. PMID: 36943885, PMCID: PMC10068818, DOI: 10.1073/pnas.2300054120.Peer-Reviewed Original ResearchConceptsOncogenic KIT mutantsStem cell factorKIT mutantsHomotypic contactsCryo-EM analysisUnexpected structural plasticityLigand stem cell factorElectron microscopy structural analysisReceptor tyrosine kinase KITOncogenic mutantsHematopoietic stem cellsKIT dimerizationTyrosine kinase KITD5 regionPlasma membraneMutational analysisMutantsExtracellular domainGerm cellsHuman cancersSomatic gainCell factorStructural plasticityStem cellsKinase KITNew Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor
Bertoletti N, Braun F, Lepage M, Möller G, Adamski J, Heine A, Klebe G, Marchais-Oberwinkler S. New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor. Journal Of Medicinal Chemistry 2016, 59: 6961-6967. PMID: 27362750, DOI: 10.1021/acs.jmedchem.6b00293.Peer-Reviewed Original ResearchConceptsCrystal structureStructure-based inhibitor designFirst crystal structureNonsteroidal inhibitorsPotent nonsteroidal inhibitorSDR enzymesInhibitor designHolo formHuman enzymeNatural variantsSteroidal ligandsTernary complexNew insightsComplexesSimilar structureEnzymeStructureType 14InhibitorsLigandsVariants