Sulfite Oxidase (SO) is a molybdenum cofactor dependent enzyme that catalyzes the oxidation of sulfite to sulfate as the final step in the degradation of the sulfur-containing amino acids, cysteine and methionine. The proposed mechanism of SO involves intramolecular electron transfer (IET) from molybdenum to the b type heme of SO and then to cytochrome c. SO is physiologically vital in human metabolism, and severe neurological damage and early death result from deficiency of SO. Sulfite oxidase deficiency is an inborn error in metabolism with symptoms that include dislocation of the ocular lenses, attenuated growth of the brain and mental retardation. The disease results either from a defect in the synthesis of the molybdenum cofactor or from various point mutations within the enzyme. The crystal structure of chicken sulfite oxidase has shown that there is a 32 Å distance between the heme and molybdenum domains, which are connected by a flexible loop (2). IET is viscosity dependent, implying that the heme domain moves closer to the molybdenum during catalysis (3). Here, we describe the kinetic effects of the P118A and P105A/P111A mutants in the loop region of human SO using laser flash photolysis and steady state methods.

1. Biochemistry 2003, 42, 12235-12242

2. Cell, 1997, 91, 973-983

3. Biochemistry 2002, 41, 5816-5821