Sulfite oxidase
sulfite oxidase | |||||||||
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ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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SUOX | |||
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Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 12: 56 – 56.01 Mb | Chr 10: 128.51 – 128.51 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Sulfite oxidase (
Sulfite oxidase is a metallo-enzyme that utilizes a molybdopterin cofactor and a heme group (in the case of animals). 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
The pyranopterin ligand which coordinates the molybdenum centre via the enedithiolate. The molybdenum centre has a square pyramidal geometry and is distinguished from the xanthine oxidase family by the orientation of the oxo group facing downwards rather than up.
Active site and mechanism
The active site of sulfite oxidase contains the
Electrons are passed one at a time from the molybdenum to the heme group which reacts with cytochrome c to reoxidize the enzyme. The electrons from this reaction enter the electron transport chain (ETC).
This reaction is generally the rate limiting reaction. Upon reaction of the enzyme with sulfite, it is reduced by 2 electrons. The negative potential seen with re-reduction of the enzyme shows the oxidized state is favoured.
Among the Mo enzyme classes, sulfite oxidase is the most easily oxidized. Although under low pH conditions the oxidative reaction become partially rate limiting.
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.[8] A G473D mutation impairs dimerization and catalysis in human sulfite oxidase.[9][10]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000139531 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049858 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 16385059.
- S2CID 6506338.
- PMID 4344230.
- PMID 16234925.
- PMID 16475804.
- PMID 17459792.
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
- Feng C, Wilson HL, Hurley JK, et al. (2003). "Essential role of conserved arginine 160 in intramolecular electron transfer in human sulfite oxidase". Biochemistry. 42 (42): 12235–42. PMID 14567685.
- Lee HF, Mak BS, Chi CS, et al. (2002). "A novel mutation in neonatal isolated sulphite oxidase deficiency". Neuropediatrics. 33 (4): 174–9. S2CID 39922068.
- Steinberg KK, Relling MV, Gallagher ML, et al. (2007). "Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada". Environ. Health Perspect. 115 (1): 158–64. PMID 17366837.
- Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. PMID 16344560.
- Wilson HL, Wilkinson SR, Rajagopalan KV (2006). "The G473D mutation impairs dimerization and catalysis in human sulfite oxidase". Biochemistry. 45 (7): 2149–60. PMID 16475804.
- Hoffmann C, Ben-Zeev B, Anikster Y, et al. (2007). "Magnetic resonance imaging and magnetic resonance spectroscopy in isolated sulfite oxidase deficiency". J. Child Neurol. 22 (10): 1214–21. S2CID 24050167.
- Johnson JL, Coyne KE, Garrett RM, et al. (2002). "Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patients". Hum. Mutat. 20 (1): 74. S2CID 45465780.
- Woo WH, Yang H, Wong KP, Halliwell B (2003). "Sulphite oxidase gene expression in human brain and in other human and rat tissues". Biochem. Biophys. Res. Commun. 305 (3): 619–23. PMID 12763039.
- Feng C, Wilson HL, Tollin G, et al. (2005). "The pathogenic human sulfite oxidase mutants G473D and A208D are defective in intramolecular electron transfer". Biochemistry. 44 (42): 13734–43. PMID 16229463.
- Tan WH, Eichler FS, Hoda S, et al. (2005). "Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature". Pediatrics. 116 (3): 757–66. S2CID 6506338.
- Astashkin AV, Johnson-Winters K, Klein EL, et al. (2008). "Structural studies of the molybdenum center of the pathogenic R160Q mutant of human sulfite oxidase by pulsed EPR spectroscopy and 17O and 33S labeling". J. Am. Chem. Soc. 130 (26): 8471–80. PMID 18529001.
- Dronov R, Kurth DG, Möhwald H, et al. (2008). "Layer-by-layer arrangement by protein-protein interaction of sulfite oxidase and cytochrome c catalyzing oxidation of sulfite". J. Am. Chem. Soc. 130 (4): 1122–3. PMID 18177044.
- Edwards MC, Johnson JL, Marriage B, et al. (1999). "Isolated sulfite oxidase deficiency: review of two cases in one family". Ophthalmology. 106 (10): 1957–61. PMID 10519592.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. PMID 15489334.
- Rudolph MJ, Johnson JL, Rajagopalan KV, Kisker C (2003). "The 1.2 A structure of the human sulfite oxidase cytochrome b(5) domain". Acta Crystallogr. D. 59 (Pt 7): 1183–91. PMID 12832761.
- Feng C, Wilson HL, Hurley JK, et al. (2003). "Role of conserved tyrosine 343 in intramolecular electron transfer in human sulfite oxidase". J. Biol. Chem. 278 (5): 2913–20. PMID 12424234.
- Neumann M, Leimkühler S (2008). "Heavy metal ions inhibit molybdoenzyme activity by binding to the dithiolene moiety of molybdopterin in Escherichia coli". FEBS J. 275 (22): 5678–89. S2CID 45452761.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Wilson HL, Rajagopalan KV (2004). "The role of tyrosine 343 in substrate binding and catalysis by human sulfite oxidase". J. Biol. Chem. 279 (15): 15105–13. PMID 14729666.
- Hakonarson H, Qu HQ, Bradfield JP, et al. (2008). "A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study". Diabetes. 57 (4): 1143–6. PMID 18198356.
External links
- Sulfite+oxidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Research Activity of Sarkar Group
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Sulfite oxidase, mitochondrial