Theoretical Study of the Mechanism for the Oxidative Half-Reaction of Copper Amine Oxidase (CAO)

The oxidative half-reaction of copper amine oxidase (CAO) has been studied quantum mechanically using hybrid density functional theory (B3LYP). After the production of H 2 O 2, two different but energetically similar mechanisms leading to the formation of ammonia and TPQ ox are suggested. In one of the mechanisms (A), protonation of the O-2 site of the cofactor TPQ occurs prior to water activation whereas in the other (B) the O-2 site of the cofactor remains unprotonated. Both of these mechanisms are divided into four steps, and the last two steps in mechanism B are further divided into two steps. Detailed comparisons are made to experimental findings and suggestions. In particular, the roles of the copper metal center and the critical Asp319 are discussed.