title: Modeling of the three-dimensional structure of the digitalis intercalating matrix in Na+/K(+)-ATPase protodimer.
abstract: Based on the knowledge that the digitalis receptor site in Na+/K(+)-ATPase is the interface between two interacting alpha-subunits of the protodimer (alpha beta)2, the present review makes an approach towards modeling the three-dimensional structure of the digitalis intercalating matrix by exploiting the information on: the primary structure and predicted membrane topology of the catalytic alpha-subunit; the determinants of the secondary, tertiary and quaternary structure of the membrane-spanning protein domains; the impact of mutational amino acid substitutions on the affinity of digitalis compounds, and the structural characteristics in potent representatives. The designed model proves its validity 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.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: K R
authors.initials: KR
authors.lastname: Repke
authors.forename: J
authors.initials: J
authors.lastname: Weiland
authors.forename: R
authors.initials: R
authors.lastname: Megges
authors.forename: R
authors.initials: R
authors.lastname: Schön
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D004070:Digitalis / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D002352:Carrier Proteins; D007364:Intercalating Agents; D008565:Membrane Proteins; D000254:Sodium-Potassium-Exchanging ATPase