Sulfite oxidase

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sulfite oxidase
Sulfite-oxidase-reaction.png
Sulfite oxidase catalyses the oxidation-reduction reaction of sulfite and water, yielding sulfate.
Identifiers
EC number 1.8.3.1
CAS number 9029-38-3
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 / QuickGO
SUOX
PDB 1mj4 EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SUOX, entrez:6821, sulfite oxidase
External IDs OMIM: 606887 MGI: 2446117 HomoloGene: 394 GeneCards: SUOX
Gene location (Human)
Chromosome 12 (human)
Chr. Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for SUOX
Genomic location for SUOX
Band 12q13.2 Start 55,997,180 bp[1]
End 56,006,641 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000456
NM_001032386
NM_001032387

NM_173733

RefSeq (protein)

NP_000447
NP_001027558
NP_001027559

NP_776094

Location (UCSC) Chr 12: 56 – 56.01 Mb Chr 12: 128.67 – 128.67 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sulfite oxidase (EC 1.8.3.1) is an enzyme in the mitochondria of all eukaryotes.[citation needed] 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.[5][6][7] 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[edit]

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[edit]

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 (MoVI). 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 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 dioxygen (O2).

Deficiency[edit]

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.[8] A G473D mutation impairs dimerization and catalysis in human sulfite oxidase.[9][10]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000139531 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049858 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ D'Errico G, Di Salle A, La Cara F, Rossi M, Cannio R (January 2006). "Identification and characterization of a novel bacterial sulfite oxidase with no heme binding domain from Deinococcus radiodurans". J. Bacteriol. 188 (2): 694–701. PMC 1347283Freely accessible. PMID 16385059. doi:10.1128/JB.188.2.694-701.2006. 
  6. ^ Tan WH, Eichler FS, Hoda S, Lee MS, Baris H, Hanley CA, Grant PE, Krishnamoorthy KS, Shih VE (September 2005). "Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature". Pediatrics. 116 (3): 757–66. PMID 16140720. doi:10.1542/peds.2004-1897. 
  7. ^ Cohen HJ, Betcher-Lange S, Kessler DL, Rajagopalan KV (December 1972). "Hepatic sulfite oxidase. Congruency in mitochondria of prosthetic groups and activity". J. Biol. Chem. 247 (23): 7759–66. PMID 4344230. 
  8. ^ Karakas E, Kisker C (November 2005). "Structural analysis of missense mutations causing isolated sulfite oxidase deficiency". Dalton Transactions (21): 3459–63. PMID 16234925. doi:10.1039/b505789m. 
  9. ^ Wilson HL, Wilkinson SR, Rajagopalan KV (February 2006). "The G473D mutation impairs dimerization and catalysis in human sulfite oxidase". Biochemistry. 45 (7): 2149–60. PMID 16475804. doi:10.1021/bi051609l. 
  10. ^ Feng C, Tollin G, Enemark JH (May 2007). "Sulfite oxidizing enzymes". Biochim. Biophys. Acta. 1774 (5): 527–39. PMC 1993547Freely accessible. PMID 17459792. doi:10.1016/j.bbapap.2007.03.006. 

Further reading[edit]

External links[edit]