Robert M. Garrett

Molecular Basis of Sulfite Oxidase Deficiency from the Structure of Sulfite Oxidase

The molybdenum-containing enzyme sulfite oxidase catalyzes the conversion of sulfite to sulfate, the terminal step in the oxidative degradation of cysteine and methionine. Deficiency of this enzyme in humans usually leads to major neurological abnormalities and early death. The crystal structure of chicken liver sulfite oxidase at 1.9 A resolution reveals that each monomer of the dimeric enzyme consists of three domains. At the active site, the Mo is penta-coordinated by three sulfur ligands, one oxo group, and one water/hydroxo. A sulfate molecule adjacent to the Mo identifies the substrate binding pocket. Four variants associated with sulfite oxidase deficiency have been identified: two mutations are near the sulfate binding site, while the other mutations occur within the domain mediating dimerization.

Molecular cloning of human liver sulfite oxidase

A 2.4 kilobase cDNA clone of human sulfite oxidase was isolated from a human liver cDNA library in lambda gt10. Comparison of three sulfite oxidase sequences to several plant and fungal nitrate reductase sequences reveals a single conserved cysteine with highly conserved flanking sequences. The conserved cysteine is postulated to be a ligand of molybdenum in sulfite oxidase and nitrate reductase.