Sulfite oxidase

Sulfite oxidase is an is_associated_with::enzyme in the is_associated_with::mitochondria of all is_associated_with::eukaryotes. It oxidizes is_associated_with::sulfite to is_associated_with::sulfate and, via is_associated_with::cytochrome c, transfers the electrons produced to the is_associated_with::electron transport chain, allowing generation of ATP in is_associated_with::oxidative phosphorylation. This is the last step in the metabolism of is_associated_with::sulfur-containing compounds and the sulfate is excreted.

Sulfite oxidase is a metallo-enzyme that utilizes a is_associated_with::molybdopterin cofactor and a is_associated_with::heme group. It is one of the cytochromes b5 and belongs to the enzyme super-family of is_associated_with::molybdenum oxotransferases that also includes is_associated_with::DMSO reductase, is_associated_with::xanthine oxidase, and is_associated_with::nitrite reductase.

In mammals, the expression levels of sulfite oxidase is high in the liver, kidney, and heart, and very low in spleen, brain, skeletal muscle, and blood.

Structure
As a is_associated_with::homodimer, sulfite oxidase contains two identical subunits with an N-terminal domain and a C-terminal domain. These two domains are connected by ten is_associated_with::amino acids forming a loop. The N-terminal domain has a is_associated_with::heme cofactor with three adjacent antiparallel is_associated_with::beta sheets and five alpha helices. The C-terminal domain hosts a molybdopterin cofactor that is surrounded by thirteen beta sheets and three alpha helices. The is_associated_with::molybdopterin cofactor has a Mo(VI) center, which is bonded to a sulfur from is_associated_with::cysteine, an ene-dithiolate from pyranopterin, and two terminal oxygens. It is at this molybdenum center that the catalytic oxidation of sulfite takes place.

Active site and mechanism
The active site of sulfite oxidase contains the is_associated_with::molybdopterin cofactor and supports molybdenum in its highest oxidation state, +6 (MoVI). In the enzyme's oxidized state, molybdenum is coordinated by a cysteine thiolate, the is_associated_with::dithiolene group of molybdopterin, and two terminal oxygen atoms (oxos). Upon reacting with sulfite, one oxygen atom is transferred to sulfite to produce sulfate, and the molybdenum center is reduced by two electrons to MoIV. Water then displaces sulfate, and the removal of two protons (H+) and two electrons (e−) returns the active site to its original state. A key feature of this oxygen atom transfer enzyme is that the oxygen atom being transferred arises from water, not from is_associated_with::dioxygen (O2).

Deficiency
Sulfite oxidase is required to metabolize the sulfur-containing amino acids cysteine and is_associated_with::methionine in foods. Lack of functional sulfite oxidase causes a disease known as sulfite oxidase deficiency. This rare but fatal disease causes neurological disorders, mental retardation, physical deformities, the degradation of the brain, and death. Reasons for the lack of functional sulfite oxidase include a genetic defect that leads to the absence of a is_associated_with::molybdopterin cofactor and is_associated_with::point mutations in the enzyme. A G473D mutation impairs dimerization and catalysis in human sulfite oxidase.