Sulfite oxidase

protein
Name = sulfite oxidase
caption =


width =
HGNCid = 11460
Symbol = SUOX
AltSymbols =
EntrezGene = 6821
OMIM = 606887
RefSeq = NM_000456
UniProt = P51687
PDB =
ECnumber =
Chromosome = 12
Arm = q
Band = 13.13
LocusSupplementaryData =

Sulfite oxidase (EC number|1.8.3.1) is a biologically important enzyme found in all living organisms. The enzyme resides in mitochondria of the cell. Mammals have large quantities of sulfite oxidase in their liver, kidney, and heart, and very little in their spleen, brain, skeletal muscle, and blood. It is responsible for the oxidation of sulfite to sulfate. This oxidation is the last step in metabolizing sulfur containing compounds. Sulfite Oxidase is a metallo-enzyme which utilizes a molydopterin cofactor and belongs to a super-family of enzymes including DMSO reductase, Xanthine Oxidase, and Nitrite Reductase.

tructure

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.

Active site and 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).

ulfite oxidase deficiency

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. In fact studies done in the Rajagopalan Laboratory at Duke University have pointed to a G473D mutation that impairs dimerization and catalysis in human sulfite oxidase. [http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi051609l]

ee also

* Bioinorganic chemistry

References

* cite journal
author = Karakas, E.; Kisker, C.
title = Structural analysis of missense mutations causing isolated sulfite oxidase deficiency
journal = Dalton Trans.
year = 2005
pages = 3459–3463
doi = 10.1039/b505789m PMID|16234925
* 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
* cite journal
author = Wilson, H.,Wilkinson S., Rajagopalan, K.
title = The G473D mutation impairs dimerization and catalysis in human sulfite oxidase.
journal = Biochemistry
year = 2006 Feb 21;45(7)
pages = 2149–60

External links

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