A theoretical study of the mechanism for the biogenesis of cofactor topaquinone in copper amine oxidases

In the present quantum chemical study, the biogenesis of the cofactor topaquinone (TPQ) has been studied using hybrid density functional theory (B3LYP). The suggested mechanism is divided into six steps and incorporates the observation of four crystallized intermediates. The experimental suggestion that the formation of the Cu(II)-peroxy species is the rate-limiting step is consistent with the results of the present study. Before the formation of the Cu(II)-peroxy species, dioxygen is suggested to first bind at the equatorial position on the copper metal center. A mechanism for the critical O-O bond cleavage is suggested, and this step is found to be driven by an unusually large exothermicity. A complex, spin-forbidden formation of H2O2 with and without the involvement of the copper metal center is discussed. The results are discussed in detail, and comparisons are made to experimental findings and suggestions.