SUBSTRATE OXIDATION IN THE ACTIVE-SITE OF XANTHINE-OXIDASE AND RELATED ENZYMES - A MODEL DENSITY-FUNCTIONAL STUDY

Gradient-corrected density functional calculations have been performed on a model for the reductive half-reaction of the molybdenum center o f xanthine oxidase related enzymes, enabling a discussion of structura l details of the Mo coordination sphere in various species involved in the reaction. On the basis of a calculated stable intermediate, we su ggest that the substrate is bound to the molybdenum site before rather than after its oxidation. The activation barrier for hydride transfer from the model substrate formaldehyde to the Mo site is calculated to be 7.7 kcal/mol. Since this reaction is predicted to be thermoneutral , the hydride transfer may occur in either direction. The complex form ed by the oxidized substrate and the active site is rather weakly boun d, supporting the postulated facile replacement of the product from th e Mo site by a water molecule.