title: Binding of ouabain and marinobufagenin leads to different structural changes in Na,K-ATPase and depends on the enzyme conformation.
abstract: Ion pump, Na,K-ATPase specifically binds cardiotonic steroids (CTS), which leads to inhibition of the enzyme activity and activation of signaling network in the cell. We have studied interaction of Na,K-ATPase with CTS of two different types - marinobufagenin and ouabain. We have shown that both CTS inhibit activity of Na,K-ATPase with the same Ki values, but binding of ouabain is sensitive to the conformation of Na,K-ATPase while binding of marinobufagenin is not. Furthermore, binding of ouabain and marinobufagenin results in different structural changes in Na,K-ATPase. Our data allow to explain the diversity of effects on the receptor function of Na,K-ATPase caused by different types of CTS.
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Vavilov Str. 32, Moscow, Russia; Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.
authors: Elizaveta A
authors: EA
authors: Klimanova
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Vavilov Str. 32, Moscow, Russia.
authors: Irina Yu
authors: IY
authors: Petrushanko
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Vavilov Str. 32, Moscow, Russia.
authors: Vladimir A
authors: VA
authors: Mitkevich
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Vavilov Str. 32, Moscow, Russia.
authors: Anastasia A
authors: AA
authors: Anashkina
authors: Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.
authors: Sergey N
authors: SN
authors: Orlov
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Vavilov Str. 32, Moscow, Russia. Electronic address: aamakarov@eimb.ru.
authors: Alexander A
authors: AA
authors: Makarov
authors: Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.
authors: Olga D
authors: OD
authors: Lopina
mesh_terms: D002018:Bufanolides / Q000378:metabolism* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D008958:Models, Molecular; D010042:Ouabain / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D002018:Bufanolides; D004791:Enzyme Inhibitors; C093896:marinobufagenin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Cardiotonic steroid; Conformational change; Isothermal titration calorimetry; Na,K-ATPase; Protein fluorescent label; Protein-ligand binding