Molybdenum center of xanthine oxidoreductase: Chiral switching and substrate coordination

PHYS 563

Predrag-Peter Ilich, pilich@csm.edu, Department of Chemistry, College of Saint Mary, 7000 Mercy Road, Omaha, NE 68106 and Russ Hille, Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210.
Analysis of structural and mechanistic parameters for the reaction of xanthine oxidoreductase, XOR, with formamide and purine substrates shows that the molybdopterin cofactor in the enzyme active site acts as a reversible chiral switch, cycling between an (S)-configuration in the fully oxidized state, Mo+6, and an (R)-configuration for the fully reduced metal center, Mo+4. This process is complemented by the induction of chirality at the substrate carbon center (pro-SCSC) and is involved in the control of coordination and, likely, de/protonation of the conjugated heterocyclic substrates in the enzyme active site (Figure). The enzyme-substrate coordination, proposed on the basis of first principles electronic structure calculations, is fully corroborated by x-ray structural data, providing an insight into possible ways of de novo design of inhibitors as well as substrates to XOR and related enzymes.

 

General Posters
7:30 PM-10:00 PM, Wednesday, March 28, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Physical Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007