A DENSITY-FUNCTIONAL STUDY OF ACTIVE-SITE MODELS FOR XANTHINE-OXIDASE

The suggestion that hydroxide is coordinated to the oxidised molybdenu m site in xanthine oxidase (XnO) is tested theoretically by computing the structures of a range of four-, five-, and six-coordinate active s ite models. The local density approximation of density functional theo ry has been used with the two experimentally verified singly bonded su lfur ligands modeled by both dithiolene, [SRCCRS](2-) (R = H and CH3), and thiolate, [CH3S](-) groups. Both ligand types give virtually iden tical results for analogous species. Based on a comparison of the comp uted M-L distances and those reported in recent EXAFS studies, it is c oncluded that both four- and six-coordination are unlikely since the o ptimized Mo-S contacts are too short or too long respectively. Of the five-coordinate MoOS(SR)(2)X models, the ones with X = [OH](-) give co mputed M-L bond lengths in excellent agreement with the reported EXAFS data while X = H2O, NH3, [CH3S](-), and O2- give relatively poor agre ement. The theoretical results imply that the active site represents a stable, preferred geometry rather than some imposed entatic state.