Aldehyde Oxidase: Reaction Mechanism and Prediction of Site of Metabolism.

ABSTRACT: Aldehyde oxidase (AO) is a molybdenum-containing enzyme involved in the clearance of drug compounds containing aldehydes and N-containing heterocyclic fragments. AO has gained considerable interest in recent years because of examples of too fast clearance of drug compounds in development. Thus, it is important to be able to predict AO-mediated drug metabolism. Therefore, we have characterized the structural and energetic aspects of different mechanisms with density functional theory using the molybdenum cofactor as a model for the reactive part of the enzyme. For a series of 6-substituted 4-quinazolinones, the trend in activation energies is the same for three tested reaction mechanisms. Using the concerted mechanism as a model for the enzymatic reaction, the transition states (TSs) for th

SUBMITTER: Montefiori M 

PROVIDER: S-EPMC6044498 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature