Flavonolignans As a Novel Class of Sodium Pump Inhibitors

0462025 - MBÚ 2017 RIV CH eng J - Článek v odborném periodiku
Kubala, M. - Čechová, P. - Geletičová, J. - Biler, M. - Štenclová, T. - Trouillas, P. - Biedermann, David
Flavonolignans As a Novel Class of Sodium Pump Inhibitors.
Frontiers in Physiology. Roč. 7, Mar 30 (2016), s. 115. ISSN 1664-042X. E-ISSN 1664-042X
Grant CEP: GA ČR(CZ) GA15-03037S
Institucionální podpora: RVO:61388971
Klíčová slova: sodium pump * Na+/K+-ATPase * flavonolignans
Kód oboru RIV: CE - Biochemie
Impakt faktor: 4.134, rok: 2016

We examined the inhibitory effects of three flavonolignans and their dehydro-derivatives, taxifolin and quercetin on the activity of the Na+/K+-ATPase (NKA). The flavonolignans silychristin, dehydrosilychristin and dehydrosilydianin inhibited NKA with IC50 of 110 +/- 40 mu M, 38 +/- 8 mu M, and 36 +/- 14 mu M, respectively. Using the methods of molecular modeling, we identified several possible binding sites for these species on NKA and proposed the possible mechanisms of inhibition. The binding to the extracellular- or cytoplasmic C-terminal sites can block the transport of cations through the plasma membrane, while the binding on the interface of cytoplasmic domains can inhibit the enzyme allosterically. Fluorescence spectroscopy experiments confirmed the interaction of these three species with the large cytoplasmic segment connecting transmembrane helices 4 and 5 (C45).
Trvalý link: http://hdl.handle.net/11104/0261638