A structural rearrangement of the Na+/K+-ATPase traps ouabain within the external ion permeation pathway.

ABSTRACT: With the use of the energy of ATP hydrolysis, the Na+/K+-ATPase is able to transport across the cell membrane Na+ and K+ against their electrochemical gradients. The enzyme is strongly inhibited by ouabain and its derivatives, some that are therapeutically used for patients with heart failure (cardiotonic steroids). Using lanthanide resonance energy transfer, we trace here the conformational changes occurring on the external side of functional Na+/K+-ATPases induced by the binding of ouabain. Changes in donor/acceptor pair distances are mainly observed within the α subunit of the enzyme. To derive a structural model matching the experimental lanthanide resonance energy transfer distances measured with bound ouabain, we carried out molecular dynamics simulations with energy restraints appli

SUBMITTER: Sanchez-Rodriguez JE 

PROVIDER: S-EPMC4457281 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature