1.13.11.20: cysteine dioxygenase
This is an abbreviated version!
For detailed information about cysteine dioxygenase, go to the full flat file.
Word Map on EC 1.13.11.20
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1.13.11.20
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taurine
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sulfinic
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non-heme
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hypotaurine
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cysteinesulfinate
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cysteamine
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cystathionine
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3-mercaptopropionate
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cys-tyr
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taut
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adenosyltransferase
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desulfhydration
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2-his-1-carboxylate
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gamma-lyase
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cupins
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2-aminoethanethiol
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medicine
- 1.13.11.20
- taurine
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sulfinic
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non-heme
- hypotaurine
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cysteinesulfinate
- cysteamine
- cystathionine
- 3-mercaptopropionate
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cys-tyr
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taut
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adenosyltransferase
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desulfhydration
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2-his-1-carboxylate
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gamma-lyase
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cupins
- 2-aminoethanethiol
- medicine
Reaction
Synonyms
3-mercaptopropionate dioxygenase, 3MDO, ADO, Arg-type CDO, BsCDO, CDO, CDO1, CDO2, CdoA, CdoB, cysteine dioxygenase, cysteine dioxygenase type 1, cysteine oxidase, Fe(II) cysteine dioxygenase, H16_A1614, H16_B1863, NP_251292, oxygenase, cysteine di-, PA2602, PCO1, PCO4
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General Information
General Information on EC 1.13.11.20 - cysteine dioxygenase
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evolution
malfunction
metabolism
physiological function
additional information
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the enzyme belongs to the 2-His-1-carboxylate family of non-heme iron containing oxidases and oxygenases
evolution
analysis of examples for two structural genomics groups of CDOs: a Bacillus subtilis Arg-type enzyme that has cysteine dioxygenase activity (BsCDO), and a Ralstonia eutropha Gln-type CDO homologue of uncharacterized activity (ReCDOhom), overview. The BsCDO active site is well conserved with mammalian CDO, and a cysteine complex captured in the active site confirms that the cysteine binding mode is also similar. The Arg position is not compatible with the mode of Cys binding seen in both Rattus norvegicus CDO and Bacillus subtilis CDO. Gln-type CDO homologues are not authentic CDOs but have substrate specificity more similar to 3-mercaptopropionate dioxygenases
evolution
structure and catalytic mechanism comparisons of nonheme iron enzymes cysteine dioxygenase with sulfoxide synthase EgtB, EC 1.14.99.50, quantum mechanics/molecular mechanics calculations, overview
evolution
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analysis of examples for two structural genomics groups of CDOs: a Bacillus subtilis Arg-type enzyme that has cysteine dioxygenase activity (BsCDO), and a Ralstonia eutropha Gln-type CDO homologue of uncharacterized activity (ReCDOhom), overview. The BsCDO active site is well conserved with mammalian CDO, and a cysteine complex captured in the active site confirms that the cysteine binding mode is also similar. The Arg position is not compatible with the mode of Cys binding seen in both Rattus norvegicus CDO and Bacillus subtilis CDO. Gln-type CDO homologues are not authentic CDOs but have substrate specificity more similar to 3-mercaptopropionate dioxygenases
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deletion of cdoA might enable increased synthesis of polythioesters
malfunction
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deletion of cdoA might enable increased synthesis of polythioesters
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malfunction
Cupriavidus necator H16 / ATCC 23440 / NCIB 10442 / S-10-1
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deletion of cdoA might enable increased synthesis of polythioesters
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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
metabolism
active-site cluster models and comparison of CDO and 3-mercaptopropionate dioxygenase MDO, EC 1.13.11.91. The enzymes have different iron(III)-superoxo-bound structures due to differences in ligand coordination. The differences in the second-coordination sphere and the position of a positively charged Arg residue result in changes in substrate positioning, mobility and enzymatic turnover. For both enzymes, the second oxygen atom transfer has the highest barriers with magnitudes of 14.2 and 15.8 kcal/mol, respectively. In CDO with its 3-His ligand system, there are close-lying singlet, triplet and quintet spin-state surfaces along the mechanism, and the reaction will be influenced by the equilibration between these spin states and the ease of spin state change
metabolism
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design of biomimetic model complexes where the 3-His coordination of theiron ion is simulated by three pyrazole donors of a trispyrazolyl borate ligand and protected cysteine represent substrate ligands. Replacement of phenyl groups attached at the 3-positions of the pyrazole units in a previous model by mesityl residues has massive consequences, as the latter arrange to a more spacious reaction pocket. The reaction with O2 proceeds much faster and the structural characterization of an iron(II) eta2-O,O-sulfinate product became possible
metabolism
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iron(II) complexes [Fe(L)(MeCN)3](SO3CF3)2 (L are two derivatives of tris(2-pyridyl)-based ligands) as models for cysteine dioxygenase. The molecular structure of one of the complexes exhibits octahedral coordination geometry, and the Fe-Npy bond lengths are similar to those in the Cys-bound FeII-CDO. The iron(II) centers of the complexes exhibit relatively high FeIII/II redox potentials E1/2 0.988-1.380 V vs. ferrocene/ferrocenium electrode. The reaction of in situ generated [Fe(L)(MeCN)(SPh)]+ with excess O2 in acetonitrile yields selectively the doubly oxygenated phenylsulfinic acid product. Both oxygen atoms of O2 are incorporated into the product. A FeIII peroxido intermediate with a rhombic S=1=2 FeIII center is involved in the reaction
metabolism
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mononuclear Co(II) complexes with the general formula [Co2+(TpR2)(CysOEt)] (R = Ph or Me, TpR2 = hydrotris(pyrazol-1-yl)borate substituted with R-groups at the 3- and 5-positions, and CysOEt is the anion of L-cysteine ethyl ester) mimic the active-site structure of substrate-bound CDO and are analogous to functional iron-based CDO models. The complexes possess five-coordinate structures featuring facially-coordinatingTpR2 and S,N-bidentate CysOEt ligands. The air-stability of the Ph-variant replicates the inactivity of cobalt-substituted CDO. The Me-variant reversibly binds O2 at reduced temperatures to yield an orange chromophore. Both are high-spin (S = 3/2) complexes. The orange chromophore is a S = 1/2 species featuring a low-spin Co(III) center bound to an end-on (eta1) superoxo ligand
metabolism
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nonheme FE(II) complex [Fe(TpMe2)(2-ATP)] , where 2-ATP is 2-aminothiophenolate, models substrate-bound cysteine dioxygenase. The complex reacts with O2 at -80°C to yield a purple intermediat that features a thiolate-ligated Fe(III) center bound to a superoxide radical, mimicking the putative structure of a key CDO intermediate
metabolism
the first target to oxidize during the iron-assisted Cys-Tyr cofactor biogenesis is Cys93
metabolism
the O2 activation mechanism suggests the binding of O2 to the metal ion followed by the attack of the distal oxygen atom on the cysteine sulfur. An alternative mechanism entails the attack of the cysteine sulfur on the proximal oxygen atom of the dioxygen moiety to form a persulfenate intermediate without any redox exchange between the metal ion and the O2 ligand. The O2 activation mechanism with a Ni-substituted active site follows the same pattern as native CDOs albeit with much higher energy barriers for the formation of the intermediates. The immediate cleavage of the persulfenate S-O bond in the alternative mechanism suggests that cysteine persulfenate might not be a true intermediate
physiological function
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CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion
physiological function
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CDO is crucial for oxidation of cysteine to cysteine sulfinic acid and therefore for sulfite production and secretion
physiological function
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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
physiological function
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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
physiological function
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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
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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
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cysteine dioxygenase is a mononuclear nonheme iron(II)-dependent enzyme critical for maintaining appropriate cysteine and taurine levels in eukaryotic systems
physiological function
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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
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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
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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
cysteine dioxygenase (CDO) helps regulate Cys levels through converting Cys to Cys sulfinic acid. The enzyme activity is in part modulated by the formation of a Cys93-Tyr157 crosslink that increases its catalytic efficiency over 10fold, mechanism, overview. The crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry
physiological function
importance of CdoA for the metabolism of the sulfur compounds 3,3'-thiodipropionic acid and 3,3'-dithiodipropionic acid by further converting their degradation product, 3-mercaptopropionate
physiological function
in the ferrous form, CDO catalyzes irreversibly the conversion of cysteine to cysteine sulfinate, incorporating both atoms of dioxygen into the product. Cysteine sulfinate is an intermediate of several pathways related to pyruvate and sulfurated metabolites, such as sulfate, taurine, and hypotaurine. The CDO performance increases in response to high cysteine levels,either through the formation of a C93-Y157 crosslink, or a diminished degradation by the ubiquitin-proteasome system
physiological function
the enzyme is involved in the metabolism of L-cysteine in the body
physiological function
the monoprotonated ES complexes with 3-mercaptopropionic acid and cysteine have different pKs. At higher pH, kcat decreases sigmoidally with a similar pK regardless of substrate. Loss of reactivity at high pH is attributed to deprotonation of tyrosine 159 and its influence on dioxygen binding. A mechanism model shows deprotonation of tyrosine 159 both blocks oxygen binding and concomitantly promotes cystine formation
physiological function
ADO catalyzes conversion of N-terminal cysteine to cysteine sulfinic acid and is related to the plant cysteine oxidases that mediate responses to hypoxia by an identical post-translational modification. In human cells ADO regulates the RGS4/5 (regulator of G-protein signalling) N-degron substrates, modulates G-protein coupled Ca2+ signals and MAPK activity, and acts on N-terminal cysteine proteins including the angiogenic cytokine IL-32. Inactivation of ADO leads to constitutive upregulation of endogenous and transfected RGS4 and RGS5 proteins irrespective of oxygen levels
physiological function
CDO knockout female mice exhibit severe defects in mammary branching morphogenesis and ductal elongation, resulting in poor lactation. CDO contributes to the luminal epithelial cell differentiation, proliferation, and apoptosis mainly through its downstream product cysteine sulfinic acid. Exogenous supplementation of cysteine sulfinic acid rescues the defects in CDO knockout mice and enhances ductal growth in wild-type mice
physiological function
CDO-/- mouse sperm demonstrates a severe lack of in vitro fertilization ability. Acrosome exocytosis and tyrosine phosphorylation profiles in response to stimuli are normal. CDO-/- sperm has a slight increase in head abnormalities. Taurine and hypotaurine concentrations in CDO-/- sperm decrease in the epididymal intraluminal fluid and sperm cytosol. No evidence of antioxidant protection against lipid peroxidation is found. CDO-/- sperm exhibits severe defects in volume regulation, swelling in response to the relatively hypo-osmotic conditions found in the female reproductive tract
physiological function
CDO1 gene is expressed in both the mold and yeast morphotypes and both morphotypes show significant CDO activity. Intracellular cysteine levels are significantly higher in the mold form of two Panamanian strains, 184AS and 186AS, equal in both mold and yeast in the class 1 Downs strain and significantly higher in yeast of the more pathogenic class 2 G217B strain
physiological function
hepatic cytosolic fraction cysteine dioxygenase activity is not responsible for the S-oxidation of the substituted cysteine, S-carboxymethyl-L-cysteine
physiological function
PCO dioxygenase activity produces Cys-sulfinic acid at the N-terminus of ERF-VII peptide, which then undergoes efficient arginylation by arginyl transferase ATE1
physiological function
transcription factor NRF2, i.e. nuclear factor-erythroid 2 p45-related factor two, promotes the accumulation of intracellular cysteine and engages the cysteine homeostatic control mechanism mediated by cysteine dioxygenase 1
physiological function
transcription factor NRF2, i.e. nuclear factor-erythroid 2 p45-related factor two, promotes the accumulation of intracellular cysteine and engages the cysteine homeostatic control mechanism mediated by cysteine dioxygenase 1
physiological function
Histoplasma capsulatum ATCC MYA-2454
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CDO1 gene is expressed in both the mold and yeast morphotypes and both morphotypes show significant CDO activity. Intracellular cysteine levels are significantly higher in the mold form of two Panamanian strains, 184AS and 186AS, equal in both mold and yeast in the class 1 Downs strain and significantly higher in yeast of the more pathogenic class 2 G217B strain
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physiological function
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the monoprotonated ES complexes with 3-mercaptopropionic acid and cysteine have different pKs. At higher pH, kcat decreases sigmoidally with a similar pK regardless of substrate. Loss of reactivity at high pH is attributed to deprotonation of tyrosine 159 and its influence on dioxygen binding. A mechanism model shows deprotonation of tyrosine 159 both blocks oxygen binding and concomitantly promotes cystine formation
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physiological function
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importance of CdoA for the metabolism of the sulfur compounds 3,3'-thiodipropionic acid and 3,3'-dithiodipropionic acid by further converting their degradation product, 3-mercaptopropionate
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physiological function
Cupriavidus necator H16 / ATCC 23440 / NCIB 10442 / S-10-1
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importance of CdoA for the metabolism of the sulfur compounds 3,3'-thiodipropionic acid and 3,3'-dithiodipropionic acid by further converting their degradation product, 3-mercaptopropionate
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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structures of iron-containing CDO model complexes, modeling, overview
additional information
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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
modeling the pH-dependence of cysteine dioxygenation
additional information
structure and mechanism leading to formation of the cysteine sulfinate product complex of a biomimetic cysteine dioxygenase model, i.e. trispyrazolylborato iron(II) cysteinato complex, overview. The enzyme contains an iron active site with an unusual 3-His ligation to the protein, which contrasts with the structural features of common non-heme iron dioxygenases
additional information
structure modeling of cysteine dioxygenase in complex with L-cysteine dianion
additional information
the BsCDO active site has a non-heme iron coordinated by three conserved residues His75, His77, and His125. Ser137, His139, andTyr141 form the catalytic triad. The bound L-Cys coordinates the iron in a bidentate fashion via its Sgamma and N atoms. Structure comparisons, overview
additional information
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the BsCDO active site has a non-heme iron coordinated by three conserved residues His75, His77, and His125. Ser137, His139, andTyr141 form the catalytic triad. The bound L-Cys coordinates the iron in a bidentate fashion via its Sgamma and N atoms. Structure comparisons, overview
additional information
the CDO enzyme active site structure comprises residues Tyr58, Arg60, His86, His88, Cys93, His140, and Tyr157, structure model
additional information
the structure of CDO, which is highly conserved across multiple species, is built on a small alpha-helical domain containing three alpha-helices at the N-terminus, followed by 13 beta-strands. These are subdivided into a main beta-sandwich domain and two beta-hairpins at the C terminus. The entire beta-sandwich is composed of seven anti-parallel beta-strands on the lower side and six anti-parallel beta-strands on the upper side. The active site comprises an iron ion, which is located in the central portion of the cupin beta-sandwhich, and is connected to the bulk solvent through a solvent-filled channel
additional information
wild-type and mutant active site structures, overview
additional information
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the BsCDO active site has a non-heme iron coordinated by three conserved residues His75, His77, and His125. Ser137, His139, andTyr141 form the catalytic triad. The bound L-Cys coordinates the iron in a bidentate fashion via its Sgamma and N atoms. Structure comparisons, overview
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