Geometry and water accessibility of the inhibitor binding site of Na⁺-pump: Pulse- and CW-EPR study.

ABSTRACT: Spin labels based on cinobufagin, a specific inhibitor of the Na,K-ATPase, have proved valuable tools to characterize the binding site of cardiotonic steroids (CTSs), which also constitutes the extracellular cation pathway. Because existing literature suggests variations in the physiological responses caused by binding of different CTSs, we extended the original set of spin-labeled inhibitors to the more potent bufalin derivatives. Positioning of the spin labels within the Na,K-ATPase site was defined and visualized by molecular docking. Although the original cinobufagin labels exhibited lower affinity, continuous-wave electron paramagnetic resonance spectra of spin-labeled bufalins and cinobufagins revealed a high degree of pairwise similarity, implying that these two types of CTS bind in

SUBMITTER: Aloi E 

PROVIDER: S-EPMC8390900 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature