Cysteine dioxygenase

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Cysteine dioxygenase
EC number
CAS number 37256-59-0
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
cysteine dioxygenase, type I
Symbol CDO1
Entrez 1036
HUGO 1795
OMIM 603943
RefSeq NM_001801
UniProt Q16878
Other data
EC number
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.

CDO reaction scheme showing cysteine sulfinic acid formation from cysteine by dioxygen incorporation

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.


External links[edit]

  1. ^ 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 5262503Freely accessible. PMID 28033001.