title: Digitalis genin activity: side-group carbonyl oxygen position is a major determinant.
abstract: The Na+,k+-adenosine triphosphatase-inhibiting activity of digitalis genins and their analogs is a function of side-group carbonyl (C = O) oxygen position. For each 2.2 angstroms that this oxygen is displaced from its position in digitoxigenin, activity drops by one order of magnitude. This quantitative relation resolves previously proposed models which have attempted to describe the molecular basis of genin activity. A multidisciplinary (crystallographic, conformational energy, synthetic, biological) approach to structure-activity relations is described.
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D004071:Digitalis Glycosides / Q000494:pharmacology*; D008968:Molecular Conformation; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004071:Digitalis Glycosides; D000254:Sodium-Potassium-Exchanging ATPase