Structure-Specificity Relationship of Cardiac Glycosides as a Substrate for Glucohydrolase II

• Published in: Chemical & pharmaceutical bulletin Vol. 48; no. 3; pp. 349 - 352
• Main Authors: TERADA, Yukimasa, MISOI, Rumi, WATANABE, Naoharu, HORNBERGER, Martin, KREIS, Wolfgang
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-03-2000; Maruzen; Japan Science and Technology Agency
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Carbohydrates - chemistry; cardenolide glucohydrolase II (CGH II); Cardenolides - metabolism; cardiac glycoside; Cardiac Glycosides - chemistry; Cardiac Glycosides - metabolism; Cardiotonic Agents - chemistry; Cardiotonic Agents - metabolism; Chemical Phenomena; Chemistry, Physical; conformation analysis; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Glucosidases - metabolism; Hydrogen Bonding; Hydrolases; Molecular Conformation; molecular mechanics; Structure-Activity Relationship; structure-specificity relationship; Steroid; Cardiotonic agent; Cardenolide; Aldose; Enzyme; Structure metabolism relation; Conformational analysis; Modeling; Disaccharide; Hydrolysis; Glycosidases; Substrate specificity; Molecular model; Force field method; Hydrolases; Glycoside; O-Glycosidases; Digitalis drug
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.48.349

Cardenolide glucohydrolase II (CGH II) is a cardenolide-specific glucohydrolase obtained from Digitalis lanata leaves. We investigated the structure-specificity relationship of several cardenolide disaccharides as a substrate for CGH II. Conformation analysis of the substrates was performed using molecular mechanics calculations. The sugar chain conformation of two inert glycosides was significantly different from that of the other glycosides. The other two glycosides, which were weak substrates of CGH II, were suggested to have an intramolecular hydrogen bond between the sugar groups. It was deduced that this hydrogen bond restricts the conformational change of the sugar chain and prevents the glycosides from enzymatic recognition.