A density functional study of active site models for xanthine oxidase

The suggestion that hydroxide is coordinated to the oxidised molybdenum site in xanthine oxidase (XnO) is tested theoretically by computing the structures of a range of four-, five-, and six-coordinate active site models. The local density approximation of density functional theory has been used with the two experimentally verified singly bonded sulfur ligands modeled by both dithiolene, [SRCCRS](2-) (R = H and CH3), and thiolate, [CH3S](-) groups. Both ligand types give virtually identical results for analogous species. Based on a comparison of the computed M-L distances and those reported in recent EXAFS studies, it is concluded that both four- and six-coordination are unlikely since the optimized 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 computed M-L bond lengths in excellent agreement with the reported EXAFS data while X = H2O, NH3, [CH3S](-), and O2- give relatively poor agreement. The theoretical results imply that the active site represents a stable, preferred geometry rather than some imposed entatic state.