Sulfite oxidase (EC 1.8.3.1) is an enzyme in the mitochondria of all eukaryotes. Mammals have large quantities of sulfite oxidase in their liver, kidney, and heart, and very little in their spleen, brain, skeletal muscle, and blood. Sulfite oxidase is one of the cytochromes b₅. It oxidises sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP.^[1][2][3] This is the last step in the metabolism of sulfur-containing compounds and the sulfate is excreted. Sulfite oxidase is a metallo-enzyme which utilises a molybdopterin cofactor and a haem group. It belongs to the enzyme super-family of oxotransferases that also includes DMSO reductase, xanthine oxidase, and nitrite reductase.

The oxidation of sulfite to sulfate carried out by sulfite oxidase.

[edit] Structure

red = N-terminal domain; purple = C-terminal domain

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

[edit] Active site and mechanism of sulfite oxidase

The proposed mechanism of sulfite oxidase.

The active site of sulfite oxidase contains the molybdopterin cofactor and supports molybdenum in its highest oxidation state, +6 (Mo^VI). In the enzyme's oxidized state, molybdenum is coordinated by a cysteine thiolate, the 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 Mo^IV. 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 dioxygen (O₂).

[edit] Sulfite oxidase deficiency

Sulfite oxidase is required to metabolize the sulfur-containing amino acids cysteine and 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 molybdopterin cofactor and point mutations in the enzyme.^[4] In fact, research at Duke University and elsewhere points to a G473D mutation that impairs dimerization and catalysis in human sulfite oxidase.^[5][6]

[edit] See also

• Bioinorganic chemistry

[edit] Further reading

• Kisker, C. “Sulfite oxidase”, Messerschimdt, A.; Huber, R.; Poulos, T.; Wieghardt, K.; eds. Handbook of Metalloproteins, vol 2; John Wiley and Sons, Ltd: New York, 2002

[edit] References

[edit] External links

• MeSH Sulfite+oxidase