Featured Publications
New 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
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