A structural view on the functional importance of the sugar moiety and steroid hydroxyls of cardiotonic steroids in binding to Na,K-ATPase.

ABSTRACT: The Na,K-ATPase is specifically inhibited by cardiotonic steroids (CTSs) like digoxin and is of significant therapeutic value in the treatment of congestive heart failure and arrhythmia. Recently, new interest has arisen in developing Na,K-ATPase inhibitors as anticancer agents. In the present study, we compare the potency and rate of inhibition as well as the reactivation of enzyme activity following inhibition by various cardiac glycosides and their aglycones at different pH values using shark Na,K-ATPase stabilized in the E2MgPi or in the E2BeFx conformations. The effects of the number and nature of various sugar residues as well as changes in the positions of hydroxyl groups on the β-side of the steroid core of cardiotonic steroids were investigated by comparing various cardiac glycosi

SUBMITTER: Cornelius F 

PROVIDER: S-EPMC3585100 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature