Cysteine dioxygenase: Difference between revisions
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'''Cysteine dioxygenase''' ('''CDO''', [[CAS number]]: 37256-59-0) is a [[mammalian]] non-[[heme]] iron [[enzyme]] that [[catalyze]]s the conversion of L-[[cysteine]] to [[cysteine sulfinic acid]] (cysteine sulfinate) | '''Cysteine dioxygenase''' ('''CDO''', [[CAS number]]: 37256-59-0) is a [[mammalian]] non-[[heme]] iron [[enzyme]] that [[catalyze]]s the conversion of L-[[cysteine]] to [[cysteine sulfinic acid]] (cysteine sulfinate) via the incorporation of two [[dioxygen]]-derived oxygens. Large concentrations of cysteine are toxic, and have been implicated in Parkinson's and Alzheimer's. CDO is also a tumor suppressor enzyme, that helps to prevent metastases by oxidizing the protective layer of cysteine that tumors surround themselves with in order to evade chemo- and radiation-generated hydroxyl radicals. | ||
[[Image:Cysteine-dioxygenase-reaction.png|frame|none|''CDO reaction scheme showing cysteine sulfinic acid formation from cysteine by dioxygen incorporation'']] | [[Image:Cysteine-dioxygenase-reaction.png|frame|none|''CDO reaction scheme showing cysteine sulfinic acid formation from cysteine by dioxygen incorporation'']] | ||
Cysteine sulfinic acid lies at a branch-point in [[cysteine catabolism]], where it can follow two pathways resulting in the formation of [[taurine]] or [[sulfate]]. The cysteine sulfinic acid-dependent pathway of taurine metabolism follows the synthesis of [[hypotaurine]] ( | |||
'''Mechanism''' The CDO mechanism is not well understood, but has been proposed to involve [[dioxygen]](O2) binding cis to a thiolate to form reactive RS-Fe-[[superoxide]] (RS-Fe-O2•–), Fe-sulfenate (RS-O; a deprotonated [[sulfenic acid]],<ref name="pmid28033001">{{cite journal | vauthors = Villar-Acevedo G, Lugo-Mas P, Blakely MN, Rees JA, Ganas AS, Hanada EM, Kaminsky W, Kovacs JA, Brines, LM | title = Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate | journal = J. Am. Chem. Soc. | volume = 139 | issue = 1 | pages = 119-129 |date=January 2017 | pmid = 28033001 | doi = 10.1021/jacs.6b03512| pmc = 5262503 }}</ref> and [[high-valent iron]]-oxo intermediates. A reactive RS-Fe-[[superoxide]] (RS-Fe-O2•–) intermediate is also involved in the mechanism of [[Isopenicillin N synthase]] (IPNS), however, rather than form an S-O bond, IPNS catalyzes C-S bond formation via [[hydrogen atom abstraction]]. | |||
Cysteine sulfinic acid lies at a branch-point in [[cysteine catabolism]], where it can follow two pathways resulting in the formation of [[taurine]] or [[sulfate]]. The cysteine sulfinic acid-dependent pathway of taurine metabolism follows the synthesis of [[hypotaurine]] (2-aminoethane sulfinate) which is subsequently oxidized to taurine. Also, cysteine sulfinate can undergo transamination to form [[β-sulfinylpyruvate]], decomposing to form [[pyruvate]] and [[sulfite]]. | |||
== References == | == References == | ||
Latest revision as of 09:13, 25 May 2018
| Cysteine dioxygenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.13.11.20 | ||||||||
| CAS number | 37256-59-0 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
| cysteine dioxygenase, type I | |
|---|---|
| Identifiers | |
| Symbol | CDO1 |
| Entrez | 1036 |
| HUGO | 1795 |
| OMIM | 603943 |
| RefSeq | NM_001801 |
| UniProt | Q16878 |
| Other data | |
| EC number | 1.13.11.20 |
| Locus | Chr. 5 q23.2 |
Cysteine dioxygenase (CDO, CAS number: 37256-59-0) is a mammalian non-heme iron enzyme that catalyzes the conversion of L-cysteine to cysteine sulfinic acid (cysteine sulfinate) via the incorporation of two dioxygen-derived oxygens. Large concentrations of cysteine are toxic, and have been implicated in Parkinson's and Alzheimer's. CDO is also a tumor suppressor enzyme, that helps to prevent metastases by oxidizing the protective layer of cysteine that tumors surround themselves with in order to evade chemo- and radiation-generated hydroxyl radicals.
Mechanism The CDO mechanism is not well understood, but has been proposed to involve dioxygen(O2) binding cis to a thiolate to form reactive RS-Fe-superoxide (RS-Fe-O2•–), Fe-sulfenate (RS-O; a deprotonated sulfenic acid,[1] and high-valent iron-oxo intermediates. A reactive RS-Fe-superoxide (RS-Fe-O2•–) intermediate is also involved in the mechanism of Isopenicillin N synthase (IPNS), however, rather than form an S-O bond, IPNS catalyzes C-S bond formation via hydrogen atom abstraction.
Cysteine sulfinic acid lies at a branch-point in cysteine catabolism, where it can follow two pathways resulting in the formation of taurine or sulfate. The cysteine sulfinic acid-dependent pathway of taurine metabolism follows the synthesis of hypotaurine (2-aminoethane sulfinate) which is subsequently oxidized to taurine. Also, cysteine sulfinate can undergo transamination to form β-sulfinylpyruvate, decomposing to form pyruvate and sulfite.
References
- Sakakibara S, Yamaguchi K, Hosokawa Y, Kohashi N, Ueda I (Feb 1976). "Purification and some properties of rat liver cysteine oxidase (cysteine dioxygenase)". Biochimica et Biophysica Acta. 422 (2): 273–9. doi:10.1016/0005-2744(76)90138-8. PMID 2307.
- Chai SC, Jerkins AA, Banik JJ, Shalev I, Pinkham JL, Uden PC, Maroney MJ (Mar 2005). "Heterologous expression, purification, and characterization of recombinant rat cysteine dioxygenase". The Journal of Biological Chemistry. 280 (11): 9865–9. doi:10.1074/jbc.M413733200. PMID 15623508.
- McCoy JG, Bailey LJ, Bitto E, Bingman CA, Aceti DJ, Fox BG, Phillips GN (Feb 2006). "Structure and mechanism of mouse cysteine dioxygenase". Proceedings of the National Academy of Sciences of the United States of America. 103 (9): 3084–9. doi:10.1073/pnas.0509262103. PMC 1413891. PMID 16492780.
External links
- CDO1 human gene location in the UCSC Genome Browser.
- CDO1 human gene details in the UCSC Genome Browser.
| This EC 1.13 enzyme-related article is a stub. You can help Wikipedia by expanding it. |
- ↑ Villar-Acevedo G, Lugo-Mas P, Blakely MN, Rees JA, Ganas AS, Hanada EM, Kaminsky W, Kovacs JA, Brines, LM (January 2017). "Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate". J. Am. Chem. Soc. 139 (1): 119–129. doi:10.1021/jacs.6b03512. PMC 5262503. PMID 28033001.