Information on EC 1.13.11.20 - cysteine dioxygenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.13.11.20
-
RECOMMENDED NAME
GeneOntology No.
cysteine dioxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
L-cysteine + O2 = 3-sulfinoalanine
show the reaction diagram
mechanism
-
L-cysteine + O2 = 3-sulfinoalanine
show the reaction diagram
Upon binding substrate, the structure of the iron site is pertubed but is still consistent with six O/N donor, indicating that cysteine may bind to the iron center, but is not bound via the sulfur atom.
-
L-cysteine + O2 = 3-sulfinoalanine
show the reaction diagram
reaction mechanism with internal electron transfer involving the ferric/ferrous enzyme forms, formation of a transient substrate-bound FeIII-superoxo species, overview
-
L-cysteine + O2 = 3-sulfinoalanine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dioxygenation
-
-
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Cysteine and methionine metabolism
-
L-cysteine degradation I
-
Metabolic pathways
-
Taurine and hypotaurine metabolism
-
taurine biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
L-cysteine:oxygen oxidoreductase
Requires Fe2+ and NAD(P)H.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3-mercaptopropionate dioxygenase
-
cysteine dioxygenase homologue
CDO
Q81CX4
-
CDO
Bacillus cereus BC2617
Q81CX4
-
-
CDO
O32085
-
CDO
-
-
CDO
-
-
CDO
Nostoc sp. PCC73102
-
-
-
CDO
P21816
-
CDO
O50490, Q9KZL0
-
CDO
Streptomyces coelicolor A3(2) SCO3035
Q9KZL0
-
-
CDO
Streptomyces coelicolor A3(2) SCO5772
O50490
-
-
CDO
Trichophyton mentagrophytes TM-10
D1MF76
-
-
CDO1
Q2PFL2
-
CDO2
Q2PFL1
-
cysteine dioxygenase
Q2PFL1, Q2PFL2
-
cysteine dioxygenase
-
-
cysteine dioxygenase
-
-
cysteine oxidase
-
-
-
-
Fe(II) cysteine dioxygenase
-
-
oxygenase, cysteine di-
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37256-59-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
BC2617 has 13.0% sequence identity with rat CDO, calculated by a BLASTP alignment using VEctor NTI; BC2617
Swissprot
Manually annotated by BRENDA team
Bacillus cereus BC2617
BC2617 has 13.0% sequence identity with rat CDO, calculated by a BLASTP alignment using VEctor NTI; BC2617
Swissprot
Manually annotated by BRENDA team
YubC has 18.7% sequence identity with rat CDO, calculated by a BLASTP alignment using Vector NTI; wild-type strain 168 and strain 168 YubC::pMUTIN4 and yubC, CDO activity is detectable in wild-type Bacillus subtilis during vegetative growth and increses to ~350% 10 h after sporulation induction. Neither yubC gene expression nor CDO catalytic activity can be detected in the yubC::pMUTIN4 strain.
Swissprot
Manually annotated by BRENDA team
gene cdo
-
-
Manually annotated by BRENDA team
strain lacking methionine sulfoxide reductase MsrA
-
-
Manually annotated by BRENDA team
strain PCC73102 posses no detectable CDO activity
-
-
Manually annotated by BRENDA team
Nostoc sp. PCC73102
strain PCC73102 posses no detectable CDO activity
-
-
Manually annotated by BRENDA team
male rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Sprague-Dawley rats, low enzyme level in rats fed a low protein diet, high enzyme level when low protein diet is supplemented with cysteine, homocystine, or methionine
-
-
Manually annotated by BRENDA team
male Sprague-Dawley rats, very low activity in animals fed a low protein diet, high level of enzyme in animals fed a protein, methionine, or cysteine rich diet
-
-
Manually annotated by BRENDA team
native and selenomethionine-substituted cysteine dioxygnease
Uniprot
Manually annotated by BRENDA team
Sprague-Dawley strain male rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley strain male rats; Wistar strain male rats
-
-
Manually annotated by BRENDA team
Wistar strain male albino rats
-
-
Manually annotated by BRENDA team
Wistar strain male rats
-
-
Manually annotated by BRENDA team
SCO3035 has 20.6% sequence identity with rat CDO, calculated by a BLASTP alignment using VEctor NTI; A3(2) SCO3035
Swissprot
Manually annotated by BRENDA team
SCO5772 has 16.4% sequence identity with rat CDO, calculated by a BLASTP alignment using Vector NTI; A3(2) SCO5772
Swissprot
Manually annotated by BRENDA team
Streptomyces coelicolor A3(2) SCO3035
SCO3035 has 20.6% sequence identity with rat CDO, calculated by a BLASTP alignment using VEctor NTI; A3(2) SCO3035
Swissprot
Manually annotated by BRENDA team
Streptomyces coelicolor A3(2) SCO5772
SCO5772 has 16.4% sequence identity with rat CDO, calculated by a BLASTP alignment using Vector NTI; A3(2) SCO5772
Swissprot
Manually annotated by BRENDA team
Trichophyton mentagrophytes TM-10
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
the enzyme belongs to the 2-His-1-carboxylate family of non-heme iron containing oxidases and oxygenases
physiological function
-
cysteine metabolism
physiological function
-
cysteine dioxygenase is a non-heme mononuclear iron enzyme that catalyzes the O2-dependent oxidation of L-cysteine to produce cysteine sulfinic acid
physiological function
-
cysteine dioxygenase is a mononuclear nonheme iron(II)-dependent enzyme critical for maintaining appropriate cysteine and taurine levels in eukaryotic systems
physiological function
-
mammalian cysteine dioxygenase is a non-heme iron protein, in its ferrous form [Fe(II)-CDO] it catalyzes the conversion of cysteine to cysteine sulfinic acid by incorporating both oxygen atoms of molecular oxygen to form the product
physiological function
-
in Histoplasma capsulatum, the enzyme is a key factor in the transition from the mycelial to yeast phase. CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion
physiological function
-
CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion
physiological function
-
CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion. In dermatophytes, CDO is a virulence factor crucial for keratin degradation, role of cysteine dioxygenase in the degradation of keratinized tissues by dermatophytes, overview. In Candida albicans upregulated expression of CDO is detected in the switch from white to opaque phenotypes [18]. In the latter, a reversible transition has been described between smooth white, dome-shaped yeast colonies (white) to circular or irregular-shaped colonies, composed of a mixture of yeast and fi lamentous cells (opaque)
physiological function
-
cysteine dioxygenase is a key enzyme involved in the homeostatic regulation of cysteine level and in production of important oxidized metabolites of cysteine such as pyruvate, sulphite, sulphate, hypotaurine, and taurine in all eukaryotic cells, CDO is crucial for oxidation of cysteine to cysteine sulphinic acid and therefore for sulphite production and secretion
physiological function
-
CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion
physiological function
-
CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion. In dermatophytes, CDO is a virulence factor crucial for keratin degradation, role of cysteine dioxygenase in the degradation of keratinized tissues by dermatophytes, overview
metabolism
-
in mammals, excess cysteine is generally degraded by oxygenation to 3-sulfino-L-alanine. The majority of cysteine sulphinic acid is then deaminated to sulphinylpyruvate, which decomposes spontaneously byreleasing inorganic sulphite. The latter compound is then further oxidized to sulphate, which is excreted for the most part from the cell. In parallel, a variable proportion of cysteine sulphinic acid is decarboxylated to hypotaurine, then further oxidized to taurine. Although cysteine can be catabolized by some non-oxidative pathways, they are of minor importance. CDO activity is regulated by concentration of cysteine, and in mammals, both have been demonstrated to be important vital factors
additional information
-
the catalytic cycle of CDO can be primed by one electron through chemical oxidation to produce CDO with ferric iron in the active site. The C93-Y157 pair of mammalian CDO is catalytically essential. The monoanionic active site contains a 5- or 6-coordinate ferrous iron with solvent molecules serving as the non-protein ligands. In the absence of substrate and/or cofactor, the reduced active site is unreactive toward O2
additional information
-
NO as a substrate analogue for O2 is used to prepare a species that mimics the geometric and electronic structures of an early reaction intermediate, analysis by magnetic circular dichroism, electron paramagnetic resonance, and electronic absorption spectroscopies as well as computational methods including density functional theory and semiempirical calculations, quantum mechanics/molecular mechanics calculations, overview. The NO adducts of Cys- and selenocysteine (Sec)-bound Fe(II)CDO exhibit virtually identical electronic properties
additional information
-
persulfenate and persulfide binding in the active site of cysteine dioxygenase, overview
additional information
-
covalent post-translational modification between the residues C93 and Y157, in close proximity to the active site, enhances the enzyme's activity. The presence of ferrous iron and oxygen is a prerequisite for C93-Y157 crosslink formation. Both the enzymatic rate of cysteine oxidation and the amount of cross-linking between C93 and Y157 increased significantly upon exposure of CDO to air/oxygen and substrate cysteine in the presence of iron in a hitherto unreported two-phase process. The non-crosslinked form has negligible enzymatic activity
additional information
-
structures of iron-containing CDO model complexes, modeling, overview
additional information
-
cysteine dioxygenase crystal structures from pH 4-9: Cys binding is minimal at below pH 5 and persulfenate formation is consistently seen at pH values between pH 5.5 and pH 7. At above pH 8, the active-site iron shifts from 4- to 5-coordinate, and Cys is bound, while dioxygen is not
additional information
-
intracellular CDO concentration is regulated at both transcriptional and posttranslational levels. Mechanism of cysteine oxygenation from iron(II)-superoxo complex, via cis- and trans-sulfoxide structure formation, to iron(IV)-oxo complex and the final product cysteine sulphinic acid
additional information
-
intracellular CDO concentration is regulated at both transcriptional and posttranslational levels, supplementation of growth medium with L-cystine induces a persistent increase in the CDO mRNA transcript level, whereas the concentration of intracellular CDO protein changes over time. Mechanism of cysteine oxygenation from iron(II)-superoxo complex, via cis- and trans-sulfoxide structure formation, to iron(IV)-oxo complex and the final product cysteine sulphinic acid
additional information
-
intracellular CDO concentration is regulated at both transcriptional and posttranslational levels. Mechanism of cysteine oxygenation from iron(II)-superoxo complex, via cis- and trans-sulfoxide structure formation, to iron(IV)-oxo complex and the final product cysteine sulphinic acid
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-mercaptopropionate + O2
3-sulfinopropanoate
show the reaction diagram
-
-
-
-
?
beta-mercaptoethanol + O2
2-hydroxyethanesulfinate
show the reaction diagram
-
slight activity
-
?
cysteamine + O2
?
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
Q16878
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
P21816
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
O50490, Q9KZL0, -
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-, O32085
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-, Q81CX4
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-, Q2PFL1, Q2PFL2
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
D1MF76, -
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
highly specific for L-cysteine
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
highly specific for L-cysteine
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
highly specific for L-cysteine
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of cysteine metabolism
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of cysteine metabolism
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
probable role in the mycelial to yeast phase transition
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
liver enzyme responds to dietary protein contents, role in regulation of intracellular levels of methionine, cysteine and glutathione
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
enzyme expression in the brain may have several possible functions, like the prevention of free radical production by the autooxidation of cysteine and dopamine
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme in sulfate production, critical regulator of cellular cysteine concentration and availability of cysteine for anabolic processes
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme in sulfate production, involved in the production of sulfate for the maintenance of a metabolic barrier against the entry of airborne xenobiotics and protein synthesis
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of cysteine catabolism, supplies substrate for taurine biosynthesis
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of taurine biosynthesis
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of taurine biosynthesis, provides substrate for transamination, regulation of intracellular cysteine level
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
regulation of intracellular cysteine concentration
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
Streptomyces coelicolor A3(2) SCO3035
Q9KZL0
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
Streptomyces coelicolor A3(2) SCO5772
O50490
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
Trichophyton mentagrophytes TM-10
D1MF76
-
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
Bacillus cereus BC2617
Q81CX4
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
D-cysteine, cystine, taurine, cystamine, cysteinesulfinic acid, glutathione, cysteic acid, S-methylcysteine and pyruvic acid do not serve as substrates
-
-
-
additional information
?
-
-
glutathione, dithiothreitol and cystine do not serve as substrates
-
-
-
additional information
?
-
-
L-cystine, D-cysteine, DL-homocysteine and cysteamine do not serve as substrates
-
-
-
additional information
?
-
-
L-cystine, D-cysteine, carboxymethyl-L-cysteine, carboxyethyl-L-cysteine, S-methyl-L-cysteine, N-acetyl-L-cysteine, DL-homocysteine and cysteamine do not serve as substrates
-
-
-
additional information
?
-
-
cysteamine does not serve as substrate, D-cysteine does not serve as substrate
-
-
-
additional information
?
-
-
cysteine dioxygenase and methionine sulfoxide reductase are working in coordination to balance cellular antioxidant level
-
-
-
additional information
?
-
-
cysteine catabolism in mammals is dependent upon cysteine dioxygenase. System for regulation of cellular cysteine levels. Evidence of abnormal or deficient CDO activity has been reported in individuals with a variety of autoimmune and neurodegenerative diseases, including rheumatoid arthritis, Parkinson’s disease, Alzheimer’s disease, and motor neuron diseases
-
-
-
additional information
?
-
-
CDO cannot catalyze the oxidation of selenocysteine
-
-
-
additional information
?
-
-
CDO exhibits high specificity for L-cysteine, displaying little or no reactivity with D-cysteine, glutathione, L-cystine, or cysteamine
-
-
-
additional information
?
-
-
cysteine dioxygenase cannot catalyze the oxidation of selenocysteine. In the Cys-bound complexes, the change of the oxidation state for the Fe center is II to III to II, while the Fe center in the Sec-bound complexes remains in the II oxidation state throughout. The competition for donation of electron density with the iron ion determines the valence change and the reaction ability
-
-
-
additional information
?
-
-
no activity with selenocysteine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of cysteine metabolism
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of cysteine metabolism
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
probable role in the mycelial to yeast phase transition
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
liver enzyme responds to dietary protein contents, role in regulation of intracellular levels of methionine, cysteine and glutathione
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
enzyme expression in the brain may have several possible functions, like the prevention of free radical production by the autooxidation of cysteine and dopamine
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme in sulfate production, critical regulator of cellular cysteine concentration and availability of cysteine for anabolic processes
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme in sulfate production, involved in the production of sulfate for the maintenance of a metabolic barrier against the entry of airborne xenobiotics and protein synthesis
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of cysteine catabolism, supplies substrate for taurine biosynthesis
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of taurine biosynthesis
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
key enzyme of taurine biosynthesis, provides substrate for transamination, regulation of intracellular cysteine level
-
-
?
L-cysteine + O2
3-sulfino-L-alanine
show the reaction diagram
-
regulation of intracellular cysteine concentration
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
L-cysteine + O2
3-sulfinoalanine
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
cysteine dioxygenase and methionine sulfoxide reductase are working in coordination to balance cellular antioxidant level
-
-
-
additional information
?
-
-
cysteine catabolism in mammals is dependent upon cysteine dioxygenase. System for regulation of cellular cysteine levels. Evidence of abnormal or deficient CDO activity has been reported in individuals with a variety of autoimmune and neurodegenerative diseases, including rheumatoid arthritis, Parkinson’s disease, Alzheimer’s disease, and motor neuron diseases
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
FAD
-
1 mol of enzyme contains about 0.1 mol of flavin
additional information
-
NADPH or NADH do not act as cosubstrates, most of added NADPH disappears from the incubation mixture during the first 10 min, while cysteinesulfinic acid remains linear for up to 30 min, the role of NADHP or NADH may be one of stabilization, as allosteric activators or other type of activating agents; unidentified heat-stable cofactor
-
additional information
-
no requirement of NAD, NADP, NADH or NADPH for the enzymic activity of protein-B. The enzymic activity of protein-B alone is extremely low, protein-A alone does not exhibit catalytic activity, however a significant activity is observed in the presence of both fractions, requirement of protein-A for the catalytic activity of protein-B
-
additional information
-
protein-A added to the assay mixture
-
additional information
-
NAD+ does not appear to be a cofactor, the role of NAD+ in the stimulation of the enzyme is unclear
-
additional information
-
enzyme uses an amino acid cofactor in the active site consisting of two cross-linked residues, cysteine 93 and tyrosine 157. Formation of the Cys-Tyr cofactor requires a transition metal cofactor Fe2+ and O2. Biogenesis of the cofactor is also strictly dependent upon the presence of substrate. In the absence of the Cys-Tyr cofactor, the enzyme possesses appreciable catalytic activity. At physiologically relevant cysteine concentrations, cofactor formation increases catalytic efficiency 10-fold
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Fe
-
Fe2+ required, 0.8-0.9 gatom of iron per 22500 g of purified protein
Fe
-
stimulation, restores activity after inhibition with EDTA
Fe
-
Fe2+ required for fully activity
Fe
-
prosthetic group
Fe
-
contains 1 atom of Fe per mol of enzyme; Fe2+ required, 0.8-0.9 gatom of iron per 22500 g of purified protein
Fe2+
-
metalloenzyme
Fe2+
-, Q81CX4
upon purification the protein is catalytically inactive, activity can be restored upon the addition of exogenous ferrous iron, with maximal activation at a ferrous iron concentration of 0.3 mM
Fe2+
-, O32085
YubC: Upon purification the protein is catalytically inactive, activity can be restored upon the addition of exogenous ferrous iron, with maximal activation at a ferrous iron concentration of 0.3 mM
Fe2+
O50490, Q9KZL0, -
upon purification the protein is catalytically inactive, activity can be restored upon the addition of exogenous ferrous iron, with maximal activation at a ferrous iron concentration of 0.3 mM; upon purification the protein is catalytically inactive, activity can be restored upon the addition of exogenous ferrous iron, with maximal activation at a ferrous iron concentration of 0.3 mM
Fe2+
-
purified human cystein dioxygenase yields a iron incorporation of about 68%; unsaturated distored tetragonal bipyramidal ferrous center with a vacant coordination site
Fe2+
-
higher kcat and lower Km value, when the enzyme is expressed in medium containing extra iron and purified in buffers lacking EDTA.
Fe2+
-
additon of 0.2 or 0.3 mM Fe2+ yields near-optimal actvity. Activity of fully purified enzyme in the absence of added Fe2+ is below 1% of that measured in the presence of 0.3 mM ferrous sulfate.
Fe2+
-
CDO is a non-heme mono-iron enzyme containing 44% ferrous iron
Fe2+
-
CDO is a mononuclear non-heme Fe2+-dependent dioxygenase
Fe2+
-
catalytically active ferrous enzyme, structure, overview
Fe2+
-
strongly bound high-spin iron(II) coordinates cysteine and homocysteine in cysteine dioxygenase, overview. CDO tightly binds iron(II) at a 3His active site. Although the cross-link between C93 and Y157 is close to the active site, it does not appear to affect iron binding. Stopped-flow measurements and Mössbauer spectral analysis, overview
Fe2+
-
a a mononuclear nonheme iron(II)-dependent enzyme. It possesses both an unusual 3-His facial ligation sphere to the iron center and a rare Cys-Tyr crosslink near the active site
Fe2+
-
required, active site bound
Fe2+
-
required for catalysis, in the Cys-bound complexes, the change of the oxidation state for the Fe center is II to III to II. Binding involves coordination with His86, His88, and His140
Fe2+
-
mammalian cysteine dioxygenase is a non-heme iron protein, in its ferrous form [Fe(II)-CDO] it catalyzes the conversion of cysteine to cysteine sulfinic acid by incorporating both oxygen atoms of molecular oxygen to form the product. A Fe(III)-superoxo rather than a Fe(IV)-oxo intermediate facilitates substrate oxidation
Iron
-
loosely bound to protein, only 10% of purified protein contains iron
Iron
-
non-heme iron
Mg
-
purified human cystein dioxygenase yields trace amounts of magnesium about 0.41%
Zn2+
-
purified human cystein dioxygenase yields a zinc incorporation of about 18.1%
Mn
-
purified human cystein dioxygenase yields trace amounts of manganese about 0.25%
additional information
-, Q81CX4
Co2+ fails to restore significant activity to purified proteins; Mn2+ fails to restore significant activity to purified proteins; Ni2+ fails to restore significant activity to purified proteins; Zn2+ fails to restore significant activity to purified proteins
additional information
-, O32085
YubC: Co2+ fails to restore significant activity to purified proteins; YubC: Mn2+ fails to restore significant activity to purified proteins; YubC: Ni2+ fails to restore significant activity to purified proteins; YubC: Zn2+ fails to restore significant activity to purified proteins
additional information
O50490, Q9KZL0, -
Co2+ fails to restore significant activity to purified proteins; Co2+ fails to restore significant activity to purified proteins; Mn2+ fails to restore significant activity to purified proteins; Mn2+ fails to restore significant activity to purified proteins; Ni2+ fails to restore significant activity to purified proteins; Ni2+ fails to restore significant activity to purified proteins; Zn2+ fails to restore significant activity to purified proteins; Zn2+ fails to restore significant activity to purified proteins
additional information
-
concentration of FeIII-CDO is highly variable and often does not exceed 5% relative to the catalytically active ferrous enzyme, ferric enzyme is catalytically inactive
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,2'-dipyridyl
-
92% inhibition at 0.1 mM
2,2'-dipyridyl
-
non preincubated protein-B: 76% inhibition at 1 mM, with cysteine preincubated protein-B: no inhibition
2,2'-dipyridyl
-
with protein-A: 100% inhibition at 0.1 mM, without protein-A: 58% inhibition at 0.1 mM
2-amino-ethanethiol
-, Q81CX4
1 x the Km for cysteine = -2.5% inhibition, 10 x the Km for cysteine = 20% inhibition
2-amino-ethanethiol
-, O32085
YubC: 1 x the Km for cysteine = 12% inhibition, 10 x the Km for cysteine = 19% inhibition
2-amino-ethanethiol
-
1 x the Km for cysteine = 8.7% inhibition, 10 x the Km for cysteine = 30% inhibition
2-amino-ethanethiol
O50490, Q9KZL0, -
SCO3035: 1 x the Km for cysteine = 7.5% inhibition, 10 x the Km for cysteine = 27% inhibition; SCO5772: 1 x the Km for cysteine = 0.9% inhibition, 10 x the Km for cysteine = 28% inhibition
2-sulfanyl-ethanol
-, Q81CX4
1 x the Km for cysteine = 4.8% inhibition, 10 x the Km for cysteine = 11% inhibition
2-sulfanyl-ethanol
-, O32085
YubC: 1 x the Km for cysteine = -0.7% inhibition, 10 x the Km for cysteine = 6.6% inhibition
2-sulfanyl-ethanol
-
1 x the Km for cysteine = 5.9% inhibition, 10 x the Km for cysteine = 13% inhibition
2-sulfanyl-ethanol
O50490, Q9KZL0, -
SCO3035: 1 x the Km for cysteine = 8.6% inhibition, 10 x the Km for cysteine = 15% inhibition; SCO5772: 1 x the Km for cysteine = 2.6% inhibition, 10 x the Km for cysteine = 13% inhibition
3,3'-thiodipropionic acid
-
-
3-Mercaptopropionic acid
-
-
3-sulfanyl-propionic acid
-, Q81CX4
1 x the Km for cysteine = 3.2% inhibition, 10 x the Km for cysteine = 12% inhibition
3-sulfanyl-propionic acid
-, O32085
YubC: 1 x the Km for cysteine = 4.7% inhibition, 10 x the Km for cysteine = 11% inhibition
3-sulfanyl-propionic acid
-
1 x the Km for cysteine = 4.9% inhibition, 10 x the Km for cysteine = 26% inhibition
3-sulfanyl-propionic acid
O50490, Q9KZL0, -
SCO3035: 1 x the Km for cysteine = 2.9% inhibition, 10 x the Km for cysteine = 11% inhibition; SCO5772: 1 x the Km for cysteine = 5.6% inhibition, 10 x the Km for cysteine = 16% inhibition
3-sulfinopropionic acid
-
-
8-hydroxyquinoline
-
59% inhibition at 0.1 mM
8-hydroxyquinoline
-
with protein-A: 100% inhibition at 0.1 mM, without protein-A: 99% inhibition at 0.1 mM
alpha-ketoglutarate
-
alpha-ketoglutarate inhibits cysteine dioxygenase with 50% inhibition at 6.8 mM
aspartic acid
-
aspartic acid decreases enzyme activity to 50% at a concentration of 1.5 mM. Replacing the sulfydryl by the uncharged hydroxyl group of serine does not affect enzyme activity.
azide
-
inhibits with a 50% activity reduction at 1.4 mM
Bathocuproine sulfonate
-
80% inhibition at 0.01 mM, 83% inhibition at 0.1 mM
Bathocuproine sulfonate
-
with protein-A: 5% inhibition at 0.1 mM, without protein-A: 38% inhibition at 0.1 mM
bathophenanthroline sulfonate
-
68% inhibition at 0.01 mM, 100% inhibition at 0.1 mM
bathophenanthroline sulfonate
-
with protein-A: 88% inhibition, without protein-A: 100% inhibition
Carboxyethyl-L-cysteine
-
53% inhibition at 1 mM
carboxymethyl-L-cysteine
-
37% inhibition at 1 mM
CdCl2
-
cells transfected with wild-type enzyme show an enhanced sensitivity to CdCl2 that is limited to cells cultured in medium with cysteine levels of 0.1 and 0.3mM
Cu2+
-
90% inhibition at 0.01 mM, 100% inhibition at 0.1 mM
cyanide
-
inhibits with a 50% actvity reduction at 2.7 mM
cysteamine
-
39% inhibition at 10 mM
cystine
-
42% inhibition at 5 mM
cytokine tumor necrosis factor-alpha
-
also TNF-alpha, down-regulation observed in hepatic and brain cells
-
D-Cysteine
-
inhibition at 1 mM
D-Cysteine
-
20% inhibition at 10 mM
D-Cysteine
-
47% inhibition at 1 mM
D-cysteinesulfinate
-
34.4% inhibition in hepatocytes from rats fed a low casein diet, 71.8% inhibition in hepatocytes from rats fed a moderate casein diet, 64.4% inhibition in hepatocytes from rats fed a high casein diet
diethyldithiocarbamate
-
no significant inhibition
diethyldithiocarbamate
-
with protein-A: not inhibitory at 0.1 mM
DL-homocysteine
-
-
DL-homocysteine
-
47% inhibition at 10 mM
DL-homocysteine
-
87% inhibition at 10 mM
DL-homocystine
-
47% inhibition at 5 mM
DL-propargylglycine
-
45.5% inhibition in hepatocytes from rats fed a high casein diet
DL-propargylglycine
-
reduces the enzyme activity in methionine-supplemented medium to the basal level, does not reduce the enzyme activity in cysteine-supplemented medium, no effect in hepatocytes cultured in basal medium
EDTA
-
totally inhibits at very low concentrations
EDTA
-
59% inhibition at 0.01 mM, 100% inhibition at 0.1 mM
EDTA
-
non preincubated protein-B: 91% inhibition at 1 mM, with cysteine preincubated protein-B: 51% inhibition at 1 mM
EDTA
-
with protein-A: 97% inhibition at 0.1 mM, with protein-A: 99% inhibition at 0.1 mM
EDTA
-
an EDTA:cysteine dioxygenase molar ratio of about 1000:1 abolish`s cysteine oxidase activity
EDTA
-
higher kcat and lower Km value, when the enzyme is expressed in medium containing extra iron and purified in buffers lacking EDTA.
EGTA
-
totally inhibits at very low concentrations
EGTA
-
with protein-A: 100% inhibition at 0.1 mM, without protein-A: 95% inhibition at 0.1 mM
Fe2+
-
50% inhibition at 0.01 mM, 100% inhibition at 0.1 mM
-
Fe2+
-
inhibits the enzyme activity of both preactivated and non-preactivated protein-B
-
homocysteine
-
50% inhibition at 6.5 mM
homocysteine
-
cysteine dioxygenase activity is reduced by 50% only when the molar ratio of homocysteine:cysteine dioxygenase reach about 30000:1
L-cysteine
-
concentrations of cysteine of 2 mM and above are inhibitory in assays of purified cysteine dioxygenase
N-acetyl-L-cysteine
-
35% inhibition at 10 mM
Neocuproine
-
with protein-A: 18% inhibition at 0.1 mM, without protein-A: slight activation at 0.1 mM
o-phenanthroline
-
totally inhibits at very low concentrations
o-phenanthroline
-
13% inhibition at 0.01 mM, 88% inhibition at 0.1 mM
o-phenanthroline
-
non-preincubated protein-B: 91% inhibition at 1 mM, with cysteine preincubated protein-B: 67% inhibition at 1 mM
o-phenanthroline
-
without protein-A: 96% inhibition at 0.1 mM, with protein A: 100% inhibition at 0.1 mM
S-carboxymethylcysteine
-
S-carboxymethylcysteine exhibits 50% inhibition at a concentration of 2.3 mM
S-methyl-L-cysteine
-
34% inhibition at 1 mM
transforming growth factor-beta
-
also TGF-beta, down-regulation observed in hepatic and brain cells
-
Mercaptopropionic acid
-
mercaptopropionic acid at a concentration of 1.2 mM inhibits cysteine dioxygenase activity by 50%
additional information
-
iodoacetamide has no effect on the enzyme activity; S-methylcysteine does not inhibit cysteine dioxygenase
-
additional information
-
inhibitors of the 26S proteasome (e.g., proteasome inhibitor 1 and lactacystin) block CDO degradation in cysteine-deficient cells but had little or no effect on CDO concentration in hepatocytes cultured with excess cysteine
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,2'-dipyridyl
-
slight activation at 0.01 mM
8-hydroxyquinoline
-
slight activation at 0.01 mM
Carboxyethyl-L-cysteine
-
at 10 mM, activation
carboxymethyl-L-cysteine
-
at 10 mM, activation
cysteamine
-
at 100 mM, activation
cysteamine
-
at a reaction time of 45 min, CDO actvity increases almost 20times in the presence of 5.8 mM cysteamine
cysteine
-
protein expression of recombinant wild-type enzyme in HepG2/C3A cells increases by 160% when extracellular cysteine levels are increased from 0 to 1 mM cysteine
D-Cysteine
-
at 10 mM, activation
diethyldithiocarbamate
-
without protein-A: 30% activation at 0.1 mM
DL-homocysteine
-
at 100 mM, slight activation
DL-homocysteine
-
-
DL-homocysteine
-
increases activity
Fe2+
-
stimulates
-
hydrocortisone
-
induces
hydroxylamine
-
activates, restores the inhibition by Fe2+
L-cysteine
-
activates the purified enzyme under anaerobic conditions
L-cysteine
-
induces the enzyme
L-cysteine
-
acts as an initial signal for regulation of the enzyme, upregulates enzyme activity; induces the enzyme
L-cysteine
-
upregulates the enzyme in hepatic and brain cells
methionine
-
induces
N-acetyl-L-cysteine
-
at 100 mM, slight activation
N-acetyl-L-cysteine
-
-
NAD(P)H
-
stimulation
NAD(P)H
-
required for fully activity
NAD+
-
stimulates
Neocuproine
-
without protein-A: slight activation at 0.1 mM
S-methyl-L-cysteine
-
at 10 mM, activation
S-methyl-L-cysteine
-
-
methionine
-
increases enzyme activity; induces
additional information
-
cysteine mediates the up-regulation of enzyme in cultured hepatocytes
-
additional information
-
with pure cysteine dioxygenase no effect of addition of NAD+ to the cysteine diosygenase is found.
-
additional information
-
effect of dietary protein or cystine on CDO expression and enzyme activity in rat liver and adipose tissue
-
additional information
-
covalent post-translational modification between the residues C93 and Y157, in close proximity to the active site, enhances the enzyme's activity. The presence of ferrous iron and oxygen is a prerequisite for C93-Y157 crosslink formation. Both the enzymatic rate of cysteine oxidation and the amount of cross-linking between C93 and Y157 increased significantly upon exposure of CDO to air/oxygen and substrate cysteine in the presence of iron in a hitherto unreported two-phase process. The non-crosslinked form has negligible enzymatic activity
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
16.6
-
beta-mercaptoethanol
-
-
0.45
-
cysteine
-
-
0.45
-
cysteine
-
in the presence of protein-A
0.67
-
cysteine
-
in the absence of protein-A
3
-
cysteine
-, O32085
YubC, measurement of cysteine sulfinic acid production is done by high-performance liquid chromatography
0.02
-
L-cysteine
-
-
0.45
-
L-cysteine
-
for purified protein
1.2
-
L-cysteine
O50490, Q9KZL0, -
SCO3035, measurement of cysteine sulfinic acid production is done by high-performance liquid chromatography
1.3
-
L-cysteine
-
-
1.5
-
L-cysteine
-
measurement of cysteine sulfinic acid production is done by high-performance liquid chromatography
2.1
-
L-cysteine
-
presence of 0.1 mol Fe2+, absence of EDTA. Cysteine sulfinic acid content is determined by ion-paired reverse-phase chromatopraphy using UV detection at 215 nm.
2.5
-
L-cysteine
-
pH 7.5, 37°C
3.1
-
L-cysteine
-
under conditions where the second substrate oxygen is saturated
3.4
-
L-cysteine
-
presence of 0.1 mol Fe2+, absence of EDTA. Cysteine sulfinic acid content is determined by ion-paired reverse-phase chromatopraphy using UV detection at 215 nm.
3.8
-
L-cysteine
O50490, Q9KZL0, -
SCO5772, measurement of cysteine sulfinic acid production is done by high-performance liquid chromatography
4.1
-
L-cysteine
-
purified recombinant enzyme, in 10 mM MES (pH 6.1) and 20 mMNaCl, at 37°C
5.7
-
L-cysteine
-, Q81CX4
measurement of cysteine sulfinic acid production is done by high-performance liquid chromatography
additional information
-
additional information
-
steady-state kinetics of recombinant CDO, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.012
-
L-cysteine
-
assay standart conditions are: the enzyme is incubated at 37°C in the presence of 62.5 mM Mes buffer (pH 6.1), 0.3 mM ferrous sulfate, 0.0125 mM bathocuproine disulfonate and 1.2 mM cysteine
0.3
-
L-cysteine
O50490, Q9KZL0, -
SCO5772
0.33
-
L-cysteine
O50490, Q9KZL0, -
SCO3035
0.39
-
L-cysteine
-, O32085
YubC
0.62
-
L-cysteine
-
-
1.7
-
L-cysteine
-
determind under saturating oxygen conditions
1.8
-
L-cysteine
-
presence of 0.1 mol Fe2+, absence of EDTA
2
-
L-cysteine
-, Q81CX4
-
3.6
-
L-cysteine
-
presence of 0.1 mol Fe2+, absence of EDTA
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.5
-
cysteamine
-
-
0.24
-
D-Cysteine
-
-
0.75
-
S-methyl-L-cysteine
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000068
-
-
in isolated hepatocytes from rats fed the diet containing a low casein level
0.00016
-
-
in hepatocytes isolated from rats fed diets containing 100 g casein/kg without sulfur amino acid supplementation
0.00017
-
-
in hepatocytes isolated from rats fed diets containing 100 g casein/kg with 2.4 g L-cystine per kg supplementation
0.0003
-
-
in isolated hepatocytes from rats fed the diet containing a moderate casein level
0.00046
-
-
in hepatocytes isolated from rats fed diets containing 100 g casein/kg with 3 g L-methionine per kg supplementation
0.00047
-
-
in isolated hepatocytes from rats fed the diet containing a high casein level
0.0012
-
-
in hepatocytes isolated from rats fed diets containing 100 g casein/kg with 8 g L-cystine per kg supplementation
0.00202
-
-
in hepatocytes isolated from rats fed diets containing 100 g casein/kg with 10 g L-methionine per kg supplementation
0.034
-
D1MF76, -
purified recombinant enzyme, in ammonium acetate buffer, pH 4.5, at 37°C
0.7
-
O50490, Q9KZL0, -
SCO5772
0.8
-
O50490, Q9KZL0, -
SCO3035
1
-
-, O32085
YubC
4.4
-
-, Q81CX4
-
additional information
-
-
-
additional information
-
-
6.31 atoms of oxygen/1000000 * min * mg protein
additional information
-
-
-
additional information
-
-
enzyme activity measured in liver homogenate, supernatant and activated supernatant with and without addition of Fe2+, NAD+ and NH2OH. Comparison of enzyme activity in liver from Wistar vs Sprague-Dawley rats in the soluble and particulate fractions of liver homogenized in sucrose vs Mes buffer. Comparison of enzyme activity in hepatocytes isolated from rats fed diets with either 100 or 300 g casein per kg
additional information
-
-
With Lineweaver-Burk plot Vmax is estimated to be 1.870 micromol cysteinesulfinate/min/mg
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
6.2
-
highest activity
6
-
O50490, Q9KZL0, -
SCO3035, pH optimum is determined by using 2-morpholinoethanesulfonic acid or Tris buffers at a final concentration of 62.5 mM
6.1
-
-, Q81CX4
pH optimum is determined by using 2-morpholinoethanesulfonic acid or Tris buffers at a final concentration of 62.5 mM
6.1
-
-
pH optimum is determined by using 2-morpholinoethanesulfonic acid or Tris buffers at a final concentration of 62.5 mM
6.1
-
O50490, Q9KZL0, -
SCO5772, pH optimum is determined by using 2-morpholinoethanesulfonic acid or Tris buffers at a final concentration of 62.5 mM
6.2
-
-, O32085
YubC, pH optimum is determined by using 2-morpholinoethanesulfonic acid or Tris buffers at a final concentration of 62.5 mM
6.8
9.5
-
for the anaerobic activation of the purified enzyme by L-cysteine
6.8
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
8.5
9
-
purified enzyme, of enzyme reaction
9
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at room temperature
37
-
-
assay at
37
-
-
activity at 37°C 2-fold higher than at 25°C
37
-
-
for the anaerobic activation of purified enzyme by L-cysteine
37
-
-
assay at
37
-
-
assay at
38
40
-
for the anaerobic activation of the purified enzyme by L-cysteine
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
37
-
activity at 37°C 2-fold higher than at 25°C
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
-
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
neuron, including the pyramidal cells of the hippocampus and the Purkinje cells of the cerebellum, the regional localization varies, with high levels of expression in the hippocampus, the dentate gyrus, the outer cortices of the brain, and the substantia nigra
Manually annotated by BRENDA team
-
barely detectable levels
Manually annotated by BRENDA team
-
lower level than in liver
Manually annotated by BRENDA team
-
hepatoblastoma cells, enzyme expression is up-regulated under hypertonic conditions
Manually annotated by BRENDA team
-
primary cell culture, high enzyme activity in cysteine rich medium
Manually annotated by BRENDA team
-
primary cell culture
Manually annotated by BRENDA team
-
CDO is found specifically in the mucus-secreting goblet cells
Manually annotated by BRENDA team
-
easily detectable levels
Manually annotated by BRENDA team
-
lower level than in liver
Manually annotated by BRENDA team
-
highest level of mRNA detected
Manually annotated by BRENDA team
-
lack of methionine sulfoxide reductase MsrA in liver of MsrA -/- mice leads to a significant drop in the cellular level of thiol groups and lowers the level of cysteine dioxygenase expression. Following selenium deficient diet applied to decrease the expression levels of selenoproteins like MsrB, the latter effect is maintained while the basal levels of thiol decreased in both wild-type strains and strains deficient for methionine dioxygenase
Manually annotated by BRENDA team
-
easily detectable levels
Manually annotated by BRENDA team
-
lower level than in liver
Manually annotated by BRENDA team
-
alveolar epithelial cells, no enzyme detected in smooth muscle cells lining the alveoli or in blood vessels within the surrounding tissue
Manually annotated by BRENDA team
-
in Streptomyces spp. CDO is expressed in the vegetative state, and an increase in its activity is detected after the initiation of conidia production
Manually annotated by BRENDA team
-
exocrine cell, but not in islet endocrine cells
Manually annotated by BRENDA team
-
detectable levels
Manually annotated by BRENDA team
-
barely detectable levels
Manually annotated by BRENDA team
-
intense staining for CDO in ductal cells of pregnant rats but not in other mammary epithelial cells or in ductal cells of non-pregnant rats
Manually annotated by BRENDA team
additional information
-
no activity in mycelium
Manually annotated by BRENDA team
additional information
-
distribution is found to be centrilobular and does not alter when the enzyme is induced with cysteine or methionine
Manually annotated by BRENDA team
additional information
-
no enzyme message observed in the spleen, heart or skeletal muscle
Manually annotated by BRENDA team
additional information
-
in Bacillus and Streptomyces spp. CDO is expressed in the vegetative state, and an increase in its activity is detected after the initiation of conidia production
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Bacillus subtilis (strain 168)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10500
-
-
gel filtration, SDS-PAGE, the estimate of molecular weight may be inaccurate because it is based on use of the iodinated protein and the assumption that iodination does not affect molecular weight
22500
-
-
SDS-PAGE, gel filtration
23000
-
-
gel filtration
23000
-
-
SDS-PAGE
23000
-
D1MF76, -
SDS-PAGE
23030
-
-
calculated from sequence of cDNA
23030
-
-
MALDI-MS; theoretical value, calculated from the primary sequence
23060
-
D1MF76, -
MALDI-TOF mass spectrometry
23500
-
-
detected by antibody for the enzyme
23500
-
-
mass spectrometry, native protein
23500
-
-, Q2PFL1, Q2PFL2
calculated from sequence
23830
-
-
calculated from deduced amino acid sequence, His-tag fusion protein
24950
-
-
mass spectrometry, thrombin cleaved enzyme
25000
-
-
SDS-PAGE, native protein
25700
-
-
SDS-PAGE, His-tag fusion protein
26800
-
-
His-tag fusion protein
68000
-
-
detection in liver whole homogenate, immunoabsorption of anti-enzyme antibodies
70000
-
-
detected by antibody for the enzyme
additional information
-
-
no 68000 Da species detected as reported in different publications
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 22500, calculated
monomer
-
1 * 10500, SDS-PAGE
monomer
-
1 * 22500, SDS-PAGE
monomer
-
1 * 25700, native and SDS-PAGE
monomer
-
1 * 23000, SDS-PAGE
additional information
-
liver enzyme is composed of 2 distinct proteins: 1. protein-B, tightly bound iron as prosthetic group, 2. protein A, modifier or activating protein
additional information
-, Q2PFL1, Q2PFL2
two bands detected, SDS-PAGE, MW: 28000 Da, 26500 Da
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
the residues Tyr-157 and Cys-93 appear to be covalently linked between Tyr-157 CE and Cys-93 SG, because these two atoms lie within 2.2 A
additional information
P21816
Cys93-Sgamma is covalently bound to Tyr157-Cepsilon2 forming a cysteinyl-tyronsine linkage.
additional information
-
two posttranslational modifications adjacent to the catalytic iron center: a thioether cross-link between Cys93 and Tyr157 and extra electron density at Cys164 which is variously explained as cystine or cysteine sulfinic acid
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
co-crystallization of L-cysteine and purified wild-type cysteine dioxygenase by the hanging drop, vapor-diffusion method at 16°C, the crystals grow as rods up to 0.2 x 0.2 x 0.8 mm in 1 week. Refinement of the crystal stucture leads to a final model with a crystallographic R-factor of 18.1% and a free R-factor of 21.5% at 2.7 A resolution.
-
enzyme with or without bound cysteine and formation of persulfenate, usage of crushed CDO crystals at 8 mg/mL in 10 mM Tris, pH 7.4, recrystallized by hanging drop vapour diffusion method, mixing of 0.0005 ml of crystal seed stock solution with 0.001 ml protein solution and 0.001 ml of reservoir solution containing 0.1 M trisodium citrate, pH 5.6, 24% PEG 4000, and 0.15 M ammonium acetate, final pH of 6.2, at room temperature, X-ray diffraction structure determination and analysis at pH 4.0-9.0 and 1.25-1.60 A resolution, overview
-
crystals are grown at 25°C by hanging-drop vapor-diffusion. The reservoir contains 20% methosylpolyethylene glycol 5000, 160 mM CaCl2, and 100 mM 2-morpholinjoethane-sulfonic acid (pH 6.5). Hanging drops consist of 2 microl of protein solution mixed with 2 microl of reservoir solution. Structure is solved to a nominal 1.75 A resolution.
-
electron paramagnetic study of substrate-O2 binding. Ordered binding of L-cysteine prior to NO and presumably O2. Upon addition of NO to cysteine dioxygenase in the presence of substrate L-cysteine, a low-spin(FeNO)7 signal with spin S of 1/2that accounts for 85% of the iron within the enzyme develops. Substitution of L-cysteine with isosteric substrate analogues cysteamine, 3-mercaptopropionic acid, and propane thiol does not produce any analogous signals.The unusual (FeNO)7, spin 1/2 electronic configuration adopted by the substrate-bound iron-nitrosyl cysteine dioxygenase is a result of the bidentate thiol/amine coordination of L-cysteine in the NO-bound active site
-
crystallization in sitting drops at 25°C using a reservoir of 0.1-0.25 M ammonium acetate, 0.1 M tri-sodium citrate, pH 5.6, with 22-26% (w/v) polyethylene glycol 4000. The co-crystals with 5 mM are grown using a reservoir of 0.15 M ammonium sulfate, 0.2 M sodium cacodylate, pH 6.5, with 26% (w/v) polyethylene glycol 8000. The crystal sturcture, solved by SAD phasing using selenomethionine-substituted protein, yields a final refined model with r = 18.0 and Rfree = 20.8 at 1.5-A resolution. Data from a co-crystallization experiment with 5 mM cysteine shows structural changes in the binding pocket, they are determined to 1.5 A resolution (final r = 19.8 and Rfree = 22.4).
P21816
purified recombinant enzyme complexed with cysteine persulfide or 3-mercaptopropionic acid persulfide, hanging drop vapor diffusion method, mixing of 0.0015 ml of 8 mg/ml protein with 0.0015 ml of reservoir solution containing 24-34% w/v PEG 4000, 100-250 mM ammonium acetate, 100 mM sodium citrate, pH 5.6, 0-4 mM dithionite, and 40 mM ligand, final pH is 6.1-6.2, 24°C, one week, X-ray diffraction structure determination and analysis at 1.63-2.05 A resolution
-
X-ray crystal structure
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
pronase destroys activity
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
rapid and irreversible inactivation under aerobic conditions, inactivation can be prevented by a distinct cytoplasmic protein, i.e. protein A
-
439542, 439546, 439548
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70°C, crude enzyme, stable for up to 4 weeks
-
-20°C, 3 months
-
0°C, no significant loss of activity after 1 month
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
using filtration, centrifugation, column chromatography on DEAE-cellulose, Sephadex G-50 and cysteine-Sepharose
-
HisTrap HP column, immobilized metal affinity chromatography, during purification two peaks of highly purified recombinant protein are found to elute: one at 10% (peak1) and the second at 20% (peak 2), kinetic data show that peak 1 has lower Km and higher Vmax values for cysteine than peak 2
-, Q81CX4
HisTrap HP column, immobilized metal affinity chromatography, during purification two peaks of highly purified recombinant protein are found to elute: one at 10% (peak1) and the second at 20%(peak 2), kinetic datat show that peak 1 has lower Km and higher Vmax values for cysteine thant peak 2.
-, O32085
standard glutathione S-transferase fusion protein purification protocol, gel-filtration chromatography after removing the glutathione S-transferase tag
-
amylose column chromatography and Superdex 200 gel filtration
-
recombinant N-terminal maltose-binding protein fusion enzyme from Escherichia coli strain BL21(DE3) by anion exchange and amylose affinity chromatography
-
recombinant N-terminal maltose-binding protein fusion enzyme from Escherichia coli strain BL21(DE3)RIPL by anion exchange and amylose affinity chromatography
-
the fusion protein is purified by immobilized metal (Ni2+) affinity chromatography. The liberated enzyme is separated from the His-8-maltose binding protein by immobilized metal affinity chromatography, further purified by gel filtration chromatography, and concentrated. EDTA is obmitted from the buffers used to purifiy enzyme for catalytic studies, and the gel filtration is not used.
-
1 ml HisTrap HP column, metal ion (nickel) affinity chromatography, gel filtration, MonoQ 4.6/100 PE ion exchange column. The thioredoxin/6x His cysteine dioxygenase fusion protein separates into two apparent isoforms that elute as two distinct peaks, one that elutes at 50 mM imidazole and one that elutes at 100 mM imidazole during metal ion affinity chromatograohy. The protein in the second peak has a specific activity, that is 50-60% less than that of the protein in the first peak. In contrast to peak 1 peak 2 elutes as two pronounced peaks (A and B) from the MonoQ column. The cysteine dioxygenase in peak A has no detectabel activity. In the the standard cysteine dioxygenase purification procedure, only the form from peak 1 is retained and further purified.
-
all buffers are supplemented with 5 mM dithiothreitol to prevent oxidation of the selenomethionine
P21816
immobilized nickel affinity chromatography
-
recombinant enzyme
-
recombinant protein using His-tag
-
recombinant thioredoxin-His6-tagged enzyme by affinity chromatography
-
recombinnat enzyme from Escherichia coli strain BL21(DE3) with cleavage of the Thx-His6 tag
-
using acetone fractionation, column chromatography on DEAE-cellulose, Sephadex G-100, hydroxylapatite, DEAE-Sephadex A-25 and Sephadex G-75
-
using acetone precipitation, first chromatography on DEAE-cellulose column, second chromatography on DEAE-cellulose column, chromatography on Sephadex G-100 column, hydroxyapatite column, DEAE-Sephadex A-25 column and Sephadex G-75 column
-
using acid treatment, ammonium sulfate fractionation and column chromatography with DEAE-cellulose. The purified enzyme is composed of two distinct proteins, it appears that one of them is a catalytic protein named protein-B having tightly bound iron as a prosthetic group, while the other is either a modifier or activating protein named protein-A. Protein-B is found to exist in both an active and an inactive form
-
using heat treatment, ammonium sulfate fractionation and column chromatography on DEAE-cellulose, Sephadex G-200 and Sephadex G-100
-
HisTrap HP column, immobilized metal affinity chromatography; HisTrap HP column, immobilized metal affinity chromatography, during purification of SCO30335 two peaks of highly purified recombinant protein are found to elute: one at 10% (peak1) and the second at 20% (peak 2), kinetic data show that peak 1 has lower Km and higher Vmax values for cysteine than peak 2
O50490, Q9KZL0, -
Ni-NTA agarose column chromatography
D1MF76, -
immobilized metal chelate affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the open reading frame of putative cysteine dioxygenase NP_832375(BC2617, Bacillus cereus ATCC 14579) is cloned and overexpressed in Escherichia coli
-, Q81CX4
the open reading frame of putative cysteine dioxygenase NP_390992(yubC, Bacillus subtilis) is cloned and overexpressed in Escherichia coli.
-, O32085
subcloned into an expression vector, pESC-TRP, for Saccharomyces cerevisiae; subcloned into an expression vector, pESC-TRP, for Saccharomyces cerevisiae
-, Q2PFL1, Q2PFL2
amplification by PCR and cloning into TA cloning vector, sequencing
-
cloned into pGEX-6p-1 expression vector, expressed in Escherichia coli Bl21(DE3), glutathione S-transferase-fused CDO is purified and GTS tag is removed by cleavage with PreScission Protease
-
cloned in plasmid pVP16 to produce the enzyme in Escherichia coli B834 pRARE2, an N-terminal fusion to a His-8-maltose binding protein
-
cloning of the gene and comparison of the gene to the known rat and human genes, sequencing, profiling of the enzyme mRNA and protein levels in mouse tissues
-
expressed in Escherichia coli BL21(DE3)pLysS cells
-
gene cdo, expression as N-terminal maltose-binding protein fusion protein in Escherichia coli strain BL21(DE3)
-
gene cdo, expression as N-terminal maltose-binding protein fusion protein in Escherichia coli strain BL21(DE3)RIPL
-
expressed as a His-tag fusion protein in Escherichia coli BL21(DE3)pLysS
-
expressed as His-tag fusion protein in Escherichia coli
-
expressed in BL21(D3)pLysS cells containing the pET-14b/CDO-ORF plasmid
-
expressed in BL21(DE3) cells
P21816
expressed in Escherichia coli strain BL21(DE3)
-
expressed in Hep-G2 cells
-
expression in Escherichia coli and HepG2/C3A cell
-
expression in Escherichia coli strain BL21(DE3)
-
expression in HepG2/C3A cell
-
gene cdo, expression of Thx-His6 ´-tagged enzyme in Escherichia coli strain BL21(DE3)
-
heterologously expressed in human HepG2/C3A cells
-
primary structure of the cDNA for liver enzyme, sequence determination
-
recombinant expression of the thioredoxin-His6-tagged enzyme
-
the open reading frame of putative cysteine dioxygenase NP_627257 (SCO30335, Streptomyces coelicolor A3(2))is cloned and overexpressed in Escherichia coli; the open reading frame of putative cysteine dioxygenase NP_629897 (SCO5772, Streptomyces coelicolor A3(2)) is cloned and overexpressed in Escherichia coli
O50490, Q9KZL0, -
expressed in Escherichia coli BL21(DE3) cells
D1MF76, -
expressed in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C164A
-
mutation of C164 shows a about 20% abatement of enzymatic activity
C164S
-
mutation of C164 shows a about 20% abatement of enzymatic activity
C93A
-
C93 mutation reduces activity to 50%, zinc content of about 45%, specific activity of Cys-93 mutants is proportional to the measured iron content.
C93S
-
C93 mutation reduces activity to 50%, zinc content of about 45%, specific activity of Cys-93 mutants is proportional to the measured iron content.
R60A
-
similar results as R60Q, R60 mutation reduces activity to 30%
R60Q
-
R60 mutation reduces activity to 30%
Y157F
-
in the gel-filtration chromatography Y157F shows an additional peak with an estimated molecular weight equivalent to a cysteine dioxygenase dimer. The results for monomer and dimer are similar. Activity reduced to 5% of the wild type activity. Zinc content of about 45%
C164A
-
mutations of nonessential residues has little effect
C93S
-
mutant can not be converted to the mature form due to the loss of the cysteine residue involved in thioether crosslink formation
H86A
-
expression of either the wild-type or a catalytically inactivated mutant H86A in HepG2/C3A cells which do not express endogenous cysteine dioxygenase protein and culture in different concentrations of extracellular cysteine. Wild-type enzyme, but not mutant H86A, is capable of reducing intracellular cysteine levels in cells incubated in physiologically relevant concentrations of cysteine. Wild-type enzyme also decreases the glutathione pool and potentiates the toxicity of CdCl2
R60A
-
mutant forms with low activity, which has a markedly decreased affinity for cysteine, probably due to the loss of the hydrogen bonding partner for the carboxylate of the substrate, forms the crosslink more slowly
S153A
-
mutations of nonessential residues has little effect
additional information
-, Q2PFL1, Q2PFL2
CDO-CSD fusion protein, cysteine dioxygenase and cysteine sulfinate decarboxylase; CDO-CSD fusion protein, cysteine dioxygenase and cysteine sulfinate decarboxylase
H86A
-
inactive mutant, leading to loss of the His that serves as a metal ligand in the active site does not form any crosslink
additional information
P21816
a selenomethionine-substituted cysteine dioxygenase is produced
additional information
-
recombinant cysteine dioxygenase protein with a thioredoxin sequence and 6 x His tagged, after purification the 6x His tag and the thioredoxin sequence are removed using factor Xa.
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
lack of methionine sulfoxide reductase MsrA in liver of MsrA -/- mice leads to a significant drop in the cellular level of thiol groups and lowers the level of cysteine dioxygenase expression. Following selenium deficient diet applied to decrease the expression levels of selenoproteins like MsrB, the latter effect is maintained while the basal levels of thiol decreased in both wild-type strains and strains deficient for methionine dioxygenase