Sulfite oxidase
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2008-05-28T19:56:22Z
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{{protein
| Name = sulfite oxidase
| caption =
| image =
| 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.
[[Image:Sulfite-oxidase-reaction.png|thumb|400px|none|The oxidation of sulfite to sulfate carried out by sulfite oxidase.]]
==Structure==
[[Image: Sulfite_oxidase.jpg|thumb|right|250px|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 acid]]s 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 sheet]]s 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==
[[Image:Sulfite-oxidase-mechanism.png|thumb|left|300px|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<sup>VI</sup>). In the enzyme's oxidized state, molybdenum is coordinated by a [[cysteine]] thiolate, the [[dithiolene]] group of molybdopterin, and two terminal oxygen atoms ([[oxo]]s). 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<sup>IV</sup>. Water then displaces sulfate, and the removal of two protons (H<sup>+</sup>) and two electrons (e<sup>-</sup>) 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]] (O<sub>2</sub>).
==Sulfite 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 [[Genetics|genetic]] defect that leads to the absence of a [[molybdopterin]] [[cofactor]] and [[point mutation]]s 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]
==See 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==
* {{MeshName|Sulfite+oxidase}}
[[Category:EC 1.8.3]]
[[Category:Metalloproteins]]
[[Category:Molybdenum compounds]]
{{1.8-enzyme-stub}}
{{Sulfur oxidoreductases}}