Mechanism of the Na,K-ATPase Inhibition by MCS Derivatives |
| |
Authors: | R?Stimac F?Kerek Email author" target="_blank">H-J?ApellEmail author |
| |
Institution: | (1) Department of Biology, University of Konstanz, Konstanz, 78457, Germany;(2) Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, Martinsried, 82152, Germany |
| |
Abstract: | The previously reported class of potent inorganic inhibitors of Na,K-ATPase, named MCS factors, was shown to inhibit not only
Na,K-ATPase but several P-type ATPases with high potency in the sub-micromolar range. These MCS factors were found to bind
to the intracellular side of the Na, K-ATPase. The inhibition is not competitive with ouabain binding, thus excluding its
role as cardiac-steroid-like inhibitor of the Na,K-ATPase. The mechanism of inhibition of Na,K-ATPase was investigated with
the fluorescent styryl dye RH421, a dye known to report changes of local electric fields in the membrane dielectric. MCS factors
interact with the Na,K-ATPase in the E1 conformation of the ion pump and induce a conformational rearrangement that causes a change of the equilibrium dissociation
constant for one of the first two intracellular cation binding sites. The MCS-inhibited state was found to have bound one
cation (H+, Na+ or K+) in one of the two unspecific binding sites, and at high Na+ concentrations another Na+ ion was bound to the highly Na+-selective ion-binding site. |
| |
Keywords: | P-type ATPase Active ion transport Ion binding Enzyme activity Fluorescence Styryl dye |
本文献已被 PubMed SpringerLink 等数据库收录! |
|