MOLECULAR-BASIS OF SULFITE OXIDASE DEFICIENCY FROM THE STRUCTURE OF SULFITE OXIDASE

The molybdenum-containing enzyme sulfite oxidase catalyzes the convers ion of sulfite to sulfate, the terminal step in the oxidative degradat ion of cysteine and methionine. Deficiency of this enzyme in humans us ually leads to major neurological abnormalities and early death. The c rystal structure of chicken liver sulfite oxidase at 1.9 Angstrom reso lution reveals that each monomer of the dimeric enzyme consists of thr ee domains. At the active site, the Mo is penta-coordinated by three s ulfur ligands, one oxo group, and one water/hydroxo. A sulfate molecul e adjacent to the Mo identifies the substrate binding pocket. Four var iants associated with sulfite oxidase deficiency have been identified: two mutations are near the sulfate binding site, while the other muta tions occur within the domain mediating dimerization.