MODELING OF THE 3-DIMENSIONAL STRUCTURE OF THE DIGITALIS INTERCALATING MATRIX IN NA+ K+-ATPASE PROTODIMER/

Based on the knowledge that the digitalis receptor site in Na+/K+-ATPa se is the interface between two interacting alpha-subunits of the prot odimer (alpha beta)(2), the present review makes an approach towards m odeling the three-dimensional structure of the digitalis intercalating matrix by exploiting the information on: the primary structure and pr edicted membrane topology of the catalytic a-subunit; the determinants of the secondary, tertiary and quaternary structure of the membrane-s panning protein domains; the impact of mutational amino acid substitut ions on the affinity of digitalis compounds, and the structural charac teristics in potent representatives. The designed model proves its val idity by allowing quantitative interpretations of the contributions of distinct amino acid side chains to the special bondings of the three structural elements of digitalis compounds.