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    Modulation of the Na,K-ATPase by Magnesium Ions
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    Department of Biology, University of Konstanz, 78464 Konstanz, Germany
    *Department of Biology, University of Konstanz, P.O. Box 635, 78464 Konstanz, Germany. Phone: +49 7531 882253. E-mail: [email protected]
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    Biochemistry

    Cite this: Biochemistry 2017, 56, 7, 1005–1016
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    https://doi.org/10.1021/acs.biochem.6b01243
    Published January 26, 2017
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    Abstract

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    Since the beginning of investigations of the Na,K-ATPase, it has been well-known that Mg2+ is an essential cofactor for activation of enzymatic ATP hydrolysis without being transported through the cell membrane. Moreover, experimental evidence has been collected through the years that shows that Mg2+ ions have a regulatory effect on ion transport by interacting with the cytoplasmic side of the ion pump. Our experiments allowed us to reveal the underlying mechanism. Mg2+ is able to bind to a site outside the membrane domain of the protein’s α subunit, close to the entrance of the access channel to the ion-binding sites, thus modifying the local concentration of the ions in the electrolyte, of which Na+, K+, and H+ are of physiological interest. The decrease in the concentration of these cations can be explained by electrostatic interaction and estimated by the Debye–Hückel theory. This effect provokes the observed apparent reduction of the binding affinity of the binding sites of the Na,K-ATPase in the presence of various Mg2+ concentrations. The presence of the bound Mg2+, however, does not affect the reaction kinetics of the transport function of the ion pump. Therefore, stopped-flow experiments could be performed to gain the first insight into the Na+ binding kinetics on the cytoplasmic side by Mg2+ concentration jump experiments.

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    • Variations of RH421 fluorescence in Mg2+ titration experiments between different enzyme preparations (Supplemental Figure 1), calculated RH421 signals of pH titrations when the Mg2+-independent contribution has been subtracted (Supplemental Figure 2), Mg2+ titration experiments in the presence of KCl (Supplemental Figure 3), and application of the Debye–Hückel theory to the simplified model of the Na,K-ATPase as shown in Figure 10A applied to selected experiments, such as a comparison of experimental and simulated Mg2+ titrations at various pHs (Supplemental Figure 4), a comparison of experimental and simulated pH titrations at various Mg2+ concentrations (Supplemental Figure 5), and Mg2+ titrations at various Na+ concentrations (Supplemental Figure 6) (PDF)

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    Biochemistry

    Cite this: Biochemistry 2017, 56, 7, 1005–1016
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biochem.6b01243
    Published January 26, 2017
    Copyright © 2017 American Chemical Society
    Request reuse permissions

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