Cycloeucalenol — obtusifoliol isomerase

Publisher Website
Google Scholar
Abstract
The molecular features of 19 synthetic substrates and ground-state analogues of cycloeucalenol, the natural substrate of cycloeucalenol.sbd.obtusifoliol isomerase, a membrane-bound enzyme specific to higher plants, and of 9 synthetic carbocationic analogues of the high-energy intermediate occurring during the reaction catalyzed by the isomerase, were related to their ability to be transformed by this enzyme (catalytical competence) and their potency as inhibitors of this enzyme. With substrates and ground-state analogues it has been possible to determine at least two critical domains: significant binding requires the presence of the 3.beta.-hydroxyl group on the ring A with the correct stereochemistry together with absence of a 4.beta.-methyl group. Moreover initial enzyme-substrate interaction appears to be dependent upon the accessibility of the 3.beta.-oxygen. Substitutions on the ring B do not preclude bindign whereas they are of great influence on substrate transformation. Modifications of the ring A domain affects binding of high-energy intermediate analogues to a much lesser extent. The effects of these and other modifications suggest that ground-state and high-energy intermediate analogues bind two different conformations of the isomerase active site.