2019
Mutational and structural studies uncover crucial amino acids determining activity and stability of 17β-HSD14
Badran M, Bertoletti N, Keils A, Heine A, Klebe G, Marchais-Oberwinkler S. Mutational and structural studies uncover crucial amino acids determining activity and stability of 17β-HSD14. The Journal Of Steroid Biochemistry And Molecular Biology 2019, 189: 135-144. PMID: 30836176, DOI: 10.1016/j.jsbmb.2019.02.009.Peer-Reviewed Original ResearchConceptsAmino acidsAdjacent monomersSite-directed mutagenesisCrucial amino acidsIndividual amino acidsEnzymatic functionCatalytic triadEnzyme variantsActive siteTerminal loopPresence of NADDisulfide bridgesNeighboring monomerCatalytic centerX-ray crystallographyDimer formationEnzyme kineticsStructural studiesTyr253His93Gln148EnzymeLatter interactionCys255Type 14
2016
First Structure–Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme
Braun F, Bertoletti N, Möller G, Adamski J, Steinmetzer T, Salah M, Abdelsamie A, van Koppen C, Heine A, Klebe G, Marchais-Oberwinkler S. First Structure–Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme. Journal Of Medicinal Chemistry 2016, 59: 10719-10737. PMID: 27933965, DOI: 10.1021/acs.jmedchem.6b01436.Peer-Reviewed Original ResearchConceptsStructure-activity relationshipsExtended H-bonding networkH-bonding networkFirst structure-activity relationshipsLigand-based approachesEnzyme active siteCrystallographic structure analysisNonsteroidal inhibitorsScaffold diversityChemical modificationHydroxyl groupsActive siteCrystal structureInteresting hitsPotent compoundsStrong affinityStructure analysisBest inhibitorCompoundsInhibitory activitySDR familyStabilization processHigh affinityAffinitySelectivity