Sulfite oxidase

sulfite oxidase
292px Sulfite oxidase catalyses the oxidation-reduction reaction of sulfite and water, yielding sulfate.
Identifiers
EC number	1.8.3.1
CAS number	Template:CAS
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Sulfite oxidase
250px PDB rendering based on 1mj4.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1MJ4
Identifiers
Symbol	SUOX
External IDs	OMIM: 606887 MGI: 2446117 HomoloGene: 394 GeneCards: SUOX Gene
EC number	1.8.3.1
Gene ontology Molecular function • sulfite oxidase activity • heme binding • molybdenum ion binding • molybdopterin cofactor binding Cellular component • mitochondrial intermembrane space • mitochondrial matrix • cytosol Biological process • sulfur amino acid metabolic process • sulfur amino acid catabolic process • response to nutrient • cellular nitrogen compound metabolic process • nitrate assimilation • small molecule metabolic process • sulfide oxidation, using sulfide:quinone oxidoreductase Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6821	211389
Ensembl	ENSG00000139531	ENSMUSG00000049858
UniProt	P51687	Q8R086
RefSeq (mRNA)	NM_000456	NM_173733
RefSeq (protein)	NP_000447	NP_776094
Location (UCSC)	Chr 12: 56 – 56.01 Mb	Chr 10: 128.67 – 128.67 Mb
PubMed search	[1]	[2]

Sulfite oxidase (EC 1.8.3.1) is an enzyme in the mitochondria of all eukaryotes. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation. This is the last step in the metabolism of sulfur-containing compounds and the sulfate is excreted.

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

File:Sulfite-oxidase-mechanism.png A proposed mechanism of the oxidation of sulfite to sulfate by 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).

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. A G473D mutation impairs dimerization and catalysis in human sulfite oxidase.

See also

• Sulfur metabolism
• Bioinorganic chemistry

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

External links

• Sulfite oxidase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Research Activity of Sarkar Group