Information on EC 1.13.11.6 - 3-hydroxyanthranilate 3,4-dioxygenase:
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EC NUMBERCOMMENTARY
1.13.11.6-

RECOMMENDED NAMEGeneOntology No.
3-hydroxyanthranilate 3,4-dioxygenaseGO:0000334

REACTIONREACTION DIAGRAMCOMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
3-hydroxyanthranilate + O2 = 2-amino-3-carboxymuconate semialdehyde
show the reaction diagram		----
3-hydroxyanthranilate + O2 = 2-amino-3-carboxymuconate semialdehyde
show the reaction diagram		mechanismHomo sapiens-439377

REACTION TYPEORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
oxidation----
redox reaction----
reduction----

PATHWAYKEGG LinkMetaCyc Link
2-nitrobenzoate degradation I-PWY-5647
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde-PWY-5651
tryptophan degradation XI (mammalian, via kynurenine)-PWY-6309
tryptophan degradation XII (Geobacillus)-PWY-6505

SYSTEMATIC NAMEIUBMB Comments
3-hydroxyanthranilate:oxygen 3,4-oxidoreductase (decyclizing)Requires Fe2+.

SYNONYMSORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
3-HADCavia porcellus--675557
3-HAORattus norvegicus--675782
3-hydroxyanthranilate 3,4-dioxygenaseRattus norvegicus--673130
3-hydroxyanthranilate 3,4-dioxygenaseBos taurusQ0VCA8-696784
3-hydroxyanthranilate oxygenase----
3-hydroxyanthranilic acid oxidase----
3-hydroxyanthranilic acid oxygenase----
3-hydroxyanthranilic acid oxygenaseRattus norvegicus--675782
3-hydroxyanthranilic oxygenase----
3HAO----
3HAOBos taurusQ0VCA8-696784
EC 1.13.1.6--formerly-
oxygenase, 3-hydroxyanthranilate 3,4-di-----

CAS REGISTRY NUMBERCOMMENTARY
9029-50-9-

ORGANISMCOMMENTARYLITERATURESEQUENCE CODESEQUENCE DB SOURCE
Bos taurus-439364, 439365, 658927--Manually annotated by BRENDA team
Bos taurus-696784Q0VCA8UniProtManually annotated by BRENDA team
Cavia porcellusHartley675557--Manually annotated by BRENDA team
Cupriavidus metalliduransrecombinantly expressed in Escherichia coli672036, 672037--Manually annotated by BRENDA team
Escherichia coli-439379--Manually annotated by BRENDA team
Homo sapiens-439377--Manually annotated by BRENDA team
Mus musculus-439376--Manually annotated by BRENDA team
Oncorhynchus mykissrainbow trout439369--Manually annotated by BRENDA team
Papio ursinusbaboon439370--Manually annotated by BRENDA team
Pseudomonas fluorescensstrain KU-7649382Q83V26SwissProtManually annotated by BRENDA team
Pseudomonas fluorescens KU-7strain KU-7649382Q83V26SwissProtManually annotated by BRENDA team
Rattus norvegicus-439366, 439367, 439368, 439371, 439375, 439378, 673130--Manually annotated by BRENDA team
Rattus norvegicusSprague Dawley439372, 439373, 439374--Manually annotated by BRENDA team
Rattus norvegicusWistar strain675782--Manually annotated by BRENDA team
Saccharomyces cerevisiae-439379P47096SwissProtManually annotated by BRENDA team
Saccharomyces cerevisiae-677020--Manually annotated by BRENDA team

GENERAL INFORMATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

SUBSTRATEPRODUCT                      REACTION DIAGRAMORGANISM UNIPROT ACCESSION NO. COMMENTARY/
Substrate		 LITERATURE/
Substrate		 COMMENTARY/
Product		 LITERATURE/
Product		 Reversibility
r=reversible
ir=irreversible
?=not specified
2-amino-3-hydroxybenzoic acid (3-hydroxyanthranilic acid) + O22,3-pyridinedicarboxylic acid (quinolinic acid) + H2O
show the reaction diagram		Bos taurusQ0VCA8-696784intermediate 2-amino-3-carboxymuconic acid semialdehyde-?
3-hydroxy-4-methylanthranilic acid + O2?
show the reaction diagram		Bos taurus--658927--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Homo sapiens--439377--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Homo sapiens--439377-439377r
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439368-439368?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439372--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439373-439373?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--675782--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Bos taurus--439364-439364?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Bos taurus--439365-439365?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Bos taurus--658927--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Oncorhynchus mykiss--439369-439369?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Papio ursinus--439370--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Cupriavidus metallidurans--672037--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Pseudomonas fluorescensQ83V26-649382--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Mus musculus--439376reacts spontaneously to quinolinic acid439376?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Escherichia coli--439379reacts spontaneously to quinolinic acid439379?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439367reacts spontaneously to quinolinic acid439367?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439371reacts spontaneously to quinolinic acid439371?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439374reacts spontaneously to quinolinic acid439374?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus--439375reacts spontaneously to quinolinic acid439375?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Saccharomyces cerevisiaeP47096-439379reacts spontaneously to quinolinic acid439379?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Cupriavidus metallidurans--672036the enzymatic product subsequently cyclizes to quinolinate-?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus-high selectivity for substrate439366reacts spontaneously to quinolinic acid439366?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus-in mammalian peripheral organs the enzyme constitutes a link in the catabolic pathway of tryptophan to NAD439366--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Papio ursinus-enzyme occurs in the metabolic pathway of the conversion of tryptophan to nicotinic acid439370--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus-biosynthetic enzyme of the endogenous excitotoxin quinolinic acid439367--?
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Saccharomyces cerevisiae-in the kynurenine pathway677020--?
4-ethyl-3-hydroxyanthranilate + O22-amino-3-carboxy-4-ethylmuconate semialdehyde
show the reaction diagram		Papio ursinus--439370-439370?
4-methyl-3-hydroxyanthranilate + O22-amino-3-carboxy-4-methylmuconate semialdehyde
show the reaction diagram		Papio ursinus--439370-439370?
4-propyl-3-hydroxyanthranilic acid + O22-amino-3-carboxy-4-propylmuconate semialdehyde
show the reaction diagram		Papio ursinus--439370-439370?
additional information?-Pseudomonas fluorescensQ83V26no detectable activity with 3-amino-4-hydroxybenzoic acid, 4-aminoresorcinol, 2-amino-m-cresol, 4-amino-3-hydroxybenzoic acid, 3-aminosalicylic acid, 6-amino-m-cresol, 3-methylcatechol, 4-methylcatechol, 1,2,4-trihydroxybenzene, 2,3-dihydroxybenzoic acid, 4-amino-m-cresol, 5-aminosalicylic acid, gentisic acid, homogentisic acid, 2-amino-4-chlorophenol, 2-amino-p-cresol, catechol, 1,2,3-trihydroxybenzene, protocatechuic acid, hydroquinone as substrates649382---

NATURAL SUBSTRATESNATURAL PRODUCTSREACTION DIAGRAMORGANISM UNIPROT ACCESSION NO.COMMENTARY SUBSTRATELITERATURE
(Substrate)		COMMENTARY PRODUCTLITERATURE
(Product)
2-amino-3-hydroxybenzoic acid (3-hydroxyanthranilic acid) + O22,3-pyridinedicarboxylic acid (quinolinic acid) + H2O
show the reaction diagram		Bos taurusQ0VCA8-696784intermediate 2-amino-3-carboxymuconic acid semialdehyde-
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Homo sapiens--439377--
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Bos taurus--658927--
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Pseudomonas fluorescensQ83V26-649382--
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus-in mammalian peripheral organs the enzyme constitutes a link in the catabolic pathway of tryptophan to NAD439366--
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Papio ursinus-enzyme occurs in the metabolic pathway of the conversion of tryptophan to nicotinic acid439370--
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Rattus norvegicus-biosynthetic enzyme of the endogenous excitotoxin quinolinic acid439367--
3-hydroxyanthranilate + O22-amino-3-carboxymuconate semialdehyde
show the reaction diagram		Saccharomyces cerevisiae-in the kynurenine pathway677020--

COFACTORORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATUREIMAGE
additional informationSaccharomyces cerevisiae-non-heme enzyme677020-

METALS and IONS ORGANISM UNIPROT ACCESSION NO.COMMENTARY LITERATURE
(NH4)2SO4Bos taurus-the most effective salt, the optimal concentration is 0.035 M439364
FeCupriavidus metallidurans-each monomer contains two iron binding sites. The catalytic iron is buried deep inside the beta-barrel with His51, Glu57, and His95 serving as ligands. The other iron site forms an FeS4 center close to the solvent surface in which the sulfur atoms are provided by Cys125, Cys128, Cys162, and Cys165. The two iron sites are separated by 24 A672037
Fe2+Bos taurus-solvent, acid and heat function to modify the protein configuration so that ferrous ions can be bound to the enzyme to generate the most active form439364
Fe2+Bos taurus-one Fe2+ per active site439365
Fe2+Rattus norvegicus-requirement439366
Fe2+Papio ursinus-requirement439370
Fe2+Homo sapiens-requirement439377
Fe2+Pseudomonas fluorescensQ83V26needed for catalytic activity649382
Fe2+Saccharomyces cerevisiae-non-heme ferrous enzyme677020
Fe3+Bos taurus-does not seem to bind to the enzyme439365
HClBos taurus-during purification of enzyme treatment with acid was used439364
MgCl2Bos taurus--439364
NaClBos taurus--439364
Ni2+Saccharomyces cerevisiae-two nickel binding sites per molecule. One of the bound nickel atoms occupies the proposed ferrous-coordinated active site677020

INHIBITORSORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
1,10-phenanthrolinePseudomonas fluorescensQ83V26Fe2+ chelator, 1 mM, complete inhibition649382 2D-image
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide methiodidePseudomonas fluorescensQ83V26carboxyl-directed reagent, 1 mM, 26% inhibition649382 2D-image
2,2'-dipyridylPseudomonas fluorescensQ83V26Fe2+ chelator, 1 mM, complete inhibition649382 2D-image
4,6-dibromo-3-hydroxyanthranilic acidRattus norvegicus-NCR-631, characterization of in vivo effects, reversible inhibition with short half-life following systematic administration439373 2D-image
4-Bromo-3-hydroxyanthranilic acidRattus norvegicus-competitive439368 2D-image
4-Bromo-3-hydroxyanthranilic acidRattus norvegicus--439375 2D-image
4-Chloro-3-hydroxyanthranilateCupriavidus metallidurans-the inactivation results in the consumption of 2 equivalents of oxygen and the production of superoxide. The inhibitor stimulates the oxidation of the active site Fe(II) to the catalytically inactive Fe(III) oxidation state. The inactivated enzyme can be reactivated by treatment with DTT and FeI(II). The nhibitor does not form an adduct with the enzyme. Four conserved cysteines are oxidized to two disulfides (Cys125-Cys128 and Cys162-Cys165) during the inactivation reaction. These results are consistent with a mechanism in which the enzyme, complexed to the inhibitor and O2, generates superoxide which subsequently dissociates, leaving the inhibitor and the oxidized iron center at the active site672036 2D-image
4-Chloro-3-hydroxyanthranilateCupriavidus metallidurans--672037 2D-image
4-Chloro-3-hydroxyanthranilateCavia porcellus-it is possible that inhibition of 3-HAD may improve neurologic status through an increased production of kynurenic acid, a non-specific inhibitor of excitatory amino acid receptors and an inhibitor of quinolinic acid neurotoxicity675557 2D-image
4-Chloro-3-hydroxyanthranilic acidRattus norvegicus-competitive439368 2D-image
4-Fluoro-3-hydroxyanthranilic acidRattus norvegicus-competitive439368 2D-image
6-chloro-3-hydroxyanthranilic acidBos taurus-5-20 mM, loss of enzymatic activity as a function of the inhibitor concentration658927 2D-image
acetaminophenRattus norvegicus--675782 2D-image
Acetylsalicylic acidRattus norvegicus--675782 2D-image
anthranilic acidBos taurus-competitive inhibition658927 2D-image
Cd2+Homo sapiens--439377 2D-image
Cd2+Pseudomonas fluorescensQ83V260.1 mM, more than 99% inhibition649382 2D-image
Co2+Pseudomonas fluorescensQ83V261 mM, 92% inhibition649382 2D-image
Cu2+Pseudomonas fluorescensQ83V260.1 mM, complete inhibition649382 2D-image
diethyl dicarbonatePseudomonas fluorescensQ83V26modifies histidine residues of catechol dioxygenases, 1 mM, 70% inhibition649382 2D-image
Dithionitrobenzoic acidPseudomonas fluorescensQ83V26cysteine-directed reagent, 1 mM, complete inhibition649382 2D-image
EDTAPseudomonas fluorescensQ83V261 mM, 99% inhibition649382 2D-image
Fe3+Pseudomonas fluorescensQ83V260.1 mM, 82% inhibition649382 2D-image
Ni2+Pseudomonas fluorescensQ83V261 mM, 82% inhibition649382 2D-image
o-methoxybenzoylalanineMus musculus-in whole-liver homogenates, but in purified enzyme preparations only in the presence of mitochondria439376 2D-image
p-chloromercuribenzoateBos taurus--439364 2D-image
p-Chloromercuriphenyl sulfonic acidPapio ursinus--439370 2D-image
Quinolinic acidBos taurus-competitive inhibition658927 2D-image
Zn2+Homo sapiens--439377 2D-image
Zn2+Pseudomonas fluorescensQ83V260.1 mM, 99% inhibition649382 2D-image
iodoacetatePseudomonas fluorescensQ83V26cysteine-directed reagent, 1 mM, 42% inhibition649382 2D-image
additional informationRattus norvegicus-not at a concentration of 0.5 mM: L-tryptophan, quinolinic acid, kynurenic acid, nicotinic acid mononucleotide, picolinic acid, phthalic acid, glutaric acid, L-aspartic acid, L-glutamic acid, N-methyl-D-aspartic acid, kainic acid439366-
additional informationHomo sapiens-not: Mn2+, Ni2+, Cu2+, Re3+, Os3+, Pb2+439377-
additional informationRattus norvegicus-both geometrical end electronic structural feature of 4,5- and 4,6-disubstituted and 4,5,6-trisubstituted 3-hydroxyanthranilic derivates play an important role in the inhibitory potency439378-

ACTIVATING COMPOUNDORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
Triton X-100Bos taurus--439364 2D-image

KM VALUE [mM]KM VALUE [mM] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
36573-hydroxy-4-methylanthranilic acidBos taurus--658927 2D-image
0.0102-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, mutant enzyme E110A672037 2D-image
0.0224-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, wild-type enzyme672037 2D-image
0.147-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, mutant enzyme R47A672037 2D-image
0.872-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, mutant enzyme R99A672037 2D-image
16193-HydroxyanthranilateBos taurus--658927 2D-image
0.002-3-hydroxyanthranilic acidRattus norvegicus--439375 2D-image
0.0030.00363-hydroxyanthranilic acidRattus norvegicus--439366, 439367 2D-image
0.0159-3-hydroxyanthranilic acidSaccharomyces cerevisiaeP47096deleted complemented strain439379 2D-image
0.0192-3-hydroxyanthranilic acidSaccharomyces cerevisiaeP47096wild-type strain439379 2D-image
0.021-3-hydroxyanthranilic acidBos taurus--439364 2D-image
0.105-3-hydroxyanthranilic acidPapio ursinus--439370 2D-image
0.011-4-ethyl-3-hydroxyanthranilic acidPapio ursinus--439370 2D-image
0.037-4-methyl-3-hydroxyanthranilic acidPapio ursinus--439370 2D-image
0.615-O2Papio ursinus--439370 2D-image
0.01-4-Propyl-3-hydroxyanthranilic acidPapio ursinus--439370 2D-image
additional information-additional informationOncorhynchus mykiss--439369-

TURNOVER NUMBER [1/s] TURNOVER NUMBER MAXIMUM[1/s] SUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.0046-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, mutant enzyme R99A672037 2D-image
0.012-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, mutant enzyme E110A672037 2D-image
0.022-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, mutant enzyme R47A672037 2D-image
25-3-HydroxyanthranilateCupriavidus metallidurans-pH 7.2, wild-type enzyme672037 2D-image
additional information-additional informationHomo sapiens--439377-

kcat/KM VALUE [1/mMs-1]kcat/KM VALUE [1/mMs-1] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

Ki VALUE [mM]Ki VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
4e-05-4-Bromo-3-hydroxyanthranilic acidRattus norvegicus-competitive439368 2D-image
3e-05-4-Chloro-3-hydroxyanthranilic acidRattus norvegicus-competitive439368 2D-image
0.00019-4-Fluoro-3-hydroxyanthranilic acidRattus norvegicus-competitive439368 2D-image
12-6-chloro-3-hydroxyanthranilic acidBos taurus--658927 2D-image
2-anthranilic acidBos taurus-for the pI 4.98 enzyme658927 2D-image
4.9-anthranilic acidBos taurus-for the pI 4.98 enzyme658927 2D-image
6.5-anthranilic acidBos taurus-for the pI 5.6 enzyme658927 2D-image
1.8-Quinolinic acidBos taurus-for the pI 5.6 enzyme658927 2D-image

IC50 VALUE [mM]IC50 VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

SPECIFIC ACTIVITY [µmol/min/mg] SPECIFIC ACTIVITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
0.0003-Rattus norvegicus-brain439367
0.0075-Rattus norvegicus-liver439367
6.8-Mus musculus--439376
7.5-Rattus norvegicus--439367
7.8-Papio ursinus--439370
7.9-Pseudomonas fluorescensQ83V263-hydroxyanthranilate as substrate, pH 6.5, 30ºC649382
115.7-Bos taurus-last purification step658927
140-Bos taurus--439365
additional information-Bos taurus-reaches a maximum after 10 min at acid pH439364
additional information-Rattus norvegicus--439371
additional information-Escherichia coli-comparison of values of wild-type and deleted complemented strains439379
additional information-Saccharomyces cerevisiaeP47096comparison of values of wild-type and deleted complemented strains439379

pH OPTIMUMpH MAXIMUMORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
6-Rattus norvegicus--439366
6-Oncorhynchus mykiss-determination on heat-reactivated extracts after inactivation439369
6.5-Rattus norvegicus--439367
6.97.4Bos taurus--658927
7.47.6Papio ursinus--439370
additional information-Rattus norvegicus-pI: 5.2439375

pH RANGEpH RANGE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
4.57Rattus norvegicus-at pH 4.5: about 70% of activity maximum, at pH 7.0: about 50% of activity maximum439366
57Rattus norvegicus--439367
57.5Oncorhynchus mykiss-determination on heat-reactivated extracts after inactivation439369
additional information-Bos taurus-at pH 3.4: the enzyme is in a form which can bind substrate but is enzymatically inactive, at pH 6.5: active form of enzyme439364

TEMPERATURE OPTIMUMTEMPERATURE OPTIMUM MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
30-Rattus norvegicus-assay at439366
37-Papio ursinus-assay at439370

TEMPERATURE RANGE TEMPERATURE MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
050Oncorhynchus mykiss-enzyme activity increased almost linearly with temperature, beyond a sharp drop439369
55-Bos taurus-activation by heating at 55°C for 5 min439364

pI VALUEpI VALUE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
4.98-Bos taurus-chromatofocusing in PBE 94 gel exchanger and polybuffer 74, pH 4-7.4658927
5.6-Bos taurus-chromatofocusing in PBE 94 gel exchanger and polybuffer 74, pH 4-7.4658927

SOURCE TISSUE ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE SOURCE
astrocyteRattus norvegicus--439372, 439373Manually annotated by BRENDA team
brainRattus norvegicus-regional distribution439366Manually annotated by BRENDA team
brainRattus norvegicus-relatively small amounts439367Manually annotated by BRENDA team
brainRattus norvegicus--439373, 439378Manually annotated by BRENDA team
hippocampusRattus norvegicus--675782Manually annotated by BRENDA team
kidneyBos taurus--439365, 696784Manually annotated by BRENDA team
kidneyRattus norvegicus-activity is low in newborn, significantly incrEases and remains elevated through the following ages673130Manually annotated by BRENDA team
liverBos taurus--439364, 658927Manually annotated by BRENDA team
liverRattus norvegicus--439367, 439368, 439371Manually annotated by BRENDA team
liverOncorhynchus mykiss--439369Manually annotated by BRENDA team
liverPapio ursinus--439370Manually annotated by BRENDA team
liverRattus norvegicus-specific activity progressively and significantly increases from newborns to 12 months of age673130Manually annotated by BRENDA team
plasmaRattus norvegicus--439373Manually annotated by BRENDA team

LOCALIZATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY GeneOntology No. LITERATURE SOURCE
cytosolMus musculus--5829439376Manually annotated by BRENDA team
solubleRattus norvegicus---439366Manually annotated by BRENDA team
solubleHomo sapiens---439377Manually annotated by BRENDA team

PDBSCOPCATHORGANISM
3fe5, downloadSCOP (3fe5)CATH (3fe5)Bos taurus
2qnk, downloadSCOP (2qnk)CATH (2qnk)Homo sapiens
1zvf, downloadSCOP (1zvf)CATH (1zvf)Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

MOLECULAR WEIGHT MOLECULAR WEIGHT MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
21240-Pseudomonas fluorescensQ83V26predicted from cDNA sequence649382
23800-Pseudomonas fluorescensQ83V26SDS-PAGE649382
32520-Bos taurus-PAGE in nondenaturing conditions, pI 4.98 enzyme658927
32570-Bos taurus-PAGE in nondenaturing conditions, pI 5.6 enzyme658927
32590-Rattus norvegicus-ion spray MS, recombinant enzyme439375
32600-Rattus norvegicus-immunoblot analysis, recombinant enzyme439371
32630-Rattus norvegicus-ion spray MS439375
3300034000Bos taurus-gel filtration658927
33000-Mus musculus--439376
33000-Bos taurus-SDS-PAGE, for the two active enzyme solutions obtained from hydroxyapatite column658927
33000-Bos taurusQ0VCA8SDS-PAGE, nondenaturating PAGE resolves two components, purified by FPLC on protein PakGlass DEAE-4 PW column, one component is N-terminally truncated annexin IV696784
34000-Bos taurus-gel filtration, readily aggregates to form inactive higher molecular weight oligomers439365
3500040000Papio ursinus-gel filtration, SDS-PAGE439370
36000-Homo sapiens-SDS-PAGE439377
3700038000Rattus norvegicus-gel filtration, SDS-PAGE, sucrose density gradient centrifugation439367

SUBUNITS ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
monomerRattus norvegicus-1 * 37000-38000, SDS-PAGE439367
monomerPapio ursinus-1 * 35000-40000, SDS-PAGE439370
monomerRattus norvegicus-1* 32589 or 32627, ion spray MS439375
monomerMus musculus-1 * 33000439376
monomerBos taurus-1 * 33000-34000, gel filtration658927
monomerBos taurusQ0VCA81 * 33000, SDS-PAGE, 286 amino acids, 2 domains that represent the dimers of the prokaryote enzyme structure which is also conserved in simple eukaryotes696784

POSTTRANSLATIONAL MODIFICATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

Crystallization/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
first vapor diffusion with sitting drop method starting from protein concentration of 10 mg/ml in 32% (NH4)2SO4, 0.1 M sodium acetate, 10 mM 2-mercaptoethanol, pH 5, subsequently, crystals can be obtained by seeding starting from fragments of first crystallization experiments using 40% (NH4)2SO4, Tris-HCl, 40 mM MgCl2, 3% MPD, pH 8 as precipitantBos taurusQ0VCA8696784
hanging drop methodCupriavidus metallidurans-672037
hanging drop-vapor diffusion method, 2.4 A resolutionSaccharomyces cerevisiae-677020

pH STABILITYpH STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
6.5-Oncorhynchus mykiss-most stable, above extremly unstable439369
10-Bos taurus-4°C, half-life: 3 days439364

TEMPERATURE STABILITYTEMPERATURE STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
04Bos taurus-stable for a month, in Tris-maleate buffer, pH 6.5658927

GENERAL STABILITYORGANISM UNIPROT ACCESSION NO.LITERATURE
stability of enzyme in crude extractOncorhynchus mykiss-439369
thawing and refreezing: crude enzyme extract at 20°C, relatively stable in presence of Fe2+, about 30% loss of activity after 2 thawingsOncorhynchus mykiss-439369

ORGANIC SOLVENT ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
additional informationBos taurus-drastic change in the Km of the enzyme in the presence of dimethylglutarate buffer439364
additional informationPapio ursinus-enzyme is not stable, when stored frozen in 20 mM Tris-maleate buffer, 1 mM dithiothreitol and 1 mM FeSO4 at pH 6.5439370

OXIDATION STABILITY ORGANISM UNIPROT ACCESSION NO. LITERATURE
No entries in this field

STORAGE STABILITY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-15°C, in 0.01 M Tris buffer, pH 7.0, 4 days, no loss of activityBos taurus-439364
-90°C, frozen in dry ice-ethanol bath, partially purified enzyme is stable for at least 1 month, purified enzyme is unstableBos taurus-439365
0°C, 0.01 M collidine chloride, 0.01 M potassium chloride, pH 6.5, about 15% loss of activity after 1 month, purified enzymeBos taurus-439365
4°C, overnight, about 75% loss of activityBos taurus-439364
0°C, 66.7 mM Tris-HCl buffer, pH 8.0, 90 min, approximately 25% loss of activityOncorhynchus mykiss-439369
25°C, 66.7 mM Tris-HCl buffer, pH 8.0, 90 min, approximately 70% loss of activityOncorhynchus mykiss-439369
4°C, overnight, 75% loss of activityPapio ursinus-439370
-80°C, as homogenate stable for 2 monthsRattus norvegicus-439366

Purification/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-Bos taurus-439364, 439365
bovine kidney homogenized in 0.1 M potassium dihydrogen phosphate buffer with 20% glycerol and 3 mM 2-mercaptoethanol, pH 7.4, centrifuged, protein fraction of supernatant that precipitates from 34-62% saturated (NH4)2SO4 is resuspended in 5 mM potassium dihydrogen phosphate buffer with 20% glycerol and 3 mM 2-mercaptoethanol, pH 7.4, dialyzed against same buffer containing protease inhibitor PMSF (0.1 mM), applied to DEAE Sephadex A-50 column, fractions with enzyme activity pooled and concentrated by precipitation with 80%-saturated (NH4)2SO4, dialyzed against 10 mM Tris-HCl with 20% glycerol and 3 mM 2-mercaptoethanol, pH 7.4, applied to Blue-Sepharose CL-4B column, concentration of active fractions by ultrafiltration through YM-10 membraneBos taurusQ0VCA8696784
succesive size exclusion and affinity columnsBos taurus-658927
-Cupriavidus metallidurans-672036, 672037
liverMus musculus-439376
-Oncorhynchus mykiss-439369
-Papio ursinus-439370
-Rattus norvegicus-439371
pure liver enzyme, partielly purified brain enzymeRattus norvegicus-439367
recombinantSaccharomyces cerevisiae-677020

Cloned/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-Escherichia coli-439379
expression in Escherichia coliHomo sapiens-439377
expression in Escherichia coliPseudomonas fluorescensQ83V26649382
expression in human embryonic kidney HEK-293Rattus norvegicus-439371, 439375
-Saccharomyces cerevisiaeP47096439379
Y3HAO protein is subcloned into the pET-28a expression vector from extracted Saccharomyces cerevisiae genomic DNA, and the Y3HAO protein is highly expressed as a soluble protein in Escherichia coli strain BL21(DE3) with a six-residueHis tag attached to its N-terminusSaccharomyces cerevisiae-677020

EXPRESSION ORGANISM UNIPROT ACCESSION NO. LITERATURE
No entries in this field

ENGINEERINGORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
E110ACupriavidus metallidurans-kcat/Km is 954fold lower than wild-type enzyme672037
R47ACupriavidus metallidurans-kcat/Km is 7440fold lower than wild-type enzyme. Mutant enzyme shows substrate inhibition672037
R99ACupriavidus metallidurans-kcat/Km is 22320fold lower than wild-type enzyme672037
H52APseudomonas fluorescensQ83V26inactive enzyme649382
H93APseudomonas fluorescensQ83V2624.8% activity of the native enzyme649382
H96APseudomonas fluorescensQ83V26inactive enzyme649382

Renatured/COMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
No entries in this field

APPLICATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
medicineRattus norvegicus-plays a role in disorders, associated with altered tissue levels of quinolinic acid439371

DISEASETITLE OF PUBLICATIONLINK TO PUBMED
Carcinoma, HepatocellularMolecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. PubMed
Huntington Disease3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. PubMed
Olivopontocerebellar AtrophiesQuinolinic acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy. PubMed
SeizuresAnticonvulsant effects of the 3-hydroxyanthranilic acid dioxygenase inhibitor NCR-631. PubMed
SeizuresDifferential expression of the astrocytic enzymes 3-hydroxyanthranilic acid oxygenase, kynurenine aminotransferase and glutamine synthetase in seizure-prone and non-epileptic mice. PubMed

REF. AUTHORS TITLE JOURNAL VOL. PAGES YEAR ORGANISMLINK TO PUBMEDSOURCE
439364Decker, R.H.; Kang, H.H.; Leach, F.R.; Henderson, L.M.Purification and properties of 3-hydroxyanthranilic acid oxidaseJ. Biol. Chem.2363076-30821961Bos taurus PubMed
439365Koontz, W.A.; Shiman, R.Beef kidney 3-hydroxyanthranilic acid oxygenase. Purification, characterization, and analysis of the assayJ. Biol. Chem.251368-3771976Bos taurus PubMed
439366Foster, A.C.; White, R.J.; Schwarcz, R.Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissue in vitroJ. Neurochem.4723-301986Rattus norvegicus PubMed
439367Okuno, E.; Köhler, C.; Schwarcz, R.Rat 3-hydroxyanthranilic acid oxygenase: purification from the liver and immunocytochemical localization in the brainJ. Neurochem.49771-7801987Rattus norvegicus PubMed
439368Walsh, J.L.; Todd, W.P.; Carpenter, B.K.; Schwarcz, R.4-Halo-3-hydroxyanthranilic acids: potent competitive inhibitors of 3-hydroxy-anthranilic acid oxygenase in vitroBiochem. Pharmacol.42985-9901991Rattus norvegicus PubMed
439369Serrano, A.E.; Nagayama, F.Liver 3-hydroxyanthranilic acid oxygenase activity in rainbow trout (Oncorhynchus mykiss)Comp. Biochem. Physiol. B99275-2801991Oncorhynchus mykiss PubMed
439370Savage, N.; Levy, P.R.The purification and some properties of 3-hydroxyanthranilate oxygenase from baboon liverInt. J. Biochem.6459-4661975Papio ursinus-
439371Malherbe, P.; Koehler, C.; Da Prada, M.; Lang, G.; Kiefer, V.; Schwarcz, R.; Lahm, H.W.; Cesura, A.M.Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenaseJ. Biol. Chem.26913792-137971994Rattus norvegicus PubMed
439372Roberts, R.C.; McCarthy, K.E.; Du, F.; Okuno, E.; Schwarcz, R.Immunocytochemical localization of the quinolinic acid synthesizing enzyme, 3-hydroxyanthranilic acid oxygenase, in the rat substantia nigraBrain Res.650229-2381994Rattus norvegicus PubMed
439373Fornstedt-Wallin, B.; Lundstrom, J.; Fredriksson, G.; Schwarcz, R.; Luthman, J.3-Hydroxyanthranilic acid accumulation following administration of the 3-hydroxyanthranilic acid 3,4-dioxygenase inhibitor NCR-631Eur. J. Pharmacol.38615-241999Rattus norvegicus PubMed
439374Roberts, R.C.; McCarthy, K.E.; Du, F.; Ottersen, O.P.; Okuno, E.; Schwarcz, R.3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatumJ. Neurosci.151150-11611995Rattus norvegicus PubMed
439375Cesura, A.M.; Alberati-Giani, D.; Buchli, R.; Broger, C.; Kohler, C.; Vilbois, F.; Lahm, H.W.; Heitz, M.P.; Malherbe, P.Molecular characterization of kynurenine pathway enzymes: 3-Hydroxyanthranilic-acid dioxygenase and kynurenine aminotransferaseAdv. Exp. Med. Biol.398477-4831996Rattus norvegicus PubMed
439376Chiarugi, A.; Moroni, F.Effects of mitochondria and o-methoxybenzoylalanine on 3-hydroxyanthranilic acid dioxygenase activity and quinolinic acid synthesisJ. Neurochem.721125-11321999Mus musculus PubMed
439377Calderone, V.; Trabucco, M.; Menin, V.; Negro, A.; Zanotti, G.Cloning of human 3-hydroxyanthranilic acid dioxygenase in Escherichia coli: characterisation of the purified enzyme and its in vitro inhibition by Zn2+Biochim. Biophys. Acta1596283-2922002Homo sapiens PubMed
439378Agrawal, V.K.; Sohgaura, R.; Khadikar, P.V.QSAR study on inhibition of brain 3-hydroxy-anthranilic acid dioxygenase (3-HAO): a molecular connectivity approachBioorg. Med. Chem.93295-32992001Rattus norvegicus PubMed
439379Kucharczyk, R.; Zagulski, M.; Rytka, J.; Herbert, C.J.The yeast gene YJR025c encodes a 3-hydroxyanthranilic acid dioxygenase and is involved in nicotinic acid biosynthesisFEBS Lett.424127-1301998Escherichia coli, Saccharomyces cerevisiae PubMed
649382Muraki, T.; Taki, M.; Hasegawa, Y.; Iwaki, H.; Lau, P.C.Prokaryotic homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase in the 2-nitrobenzoate degradation pathway of Pseudomonas fluorescens strain KU-7Appl. Environ. Microbiol.691564-15722003Pseudomonas fluorescens PubMed
658927Nandi, D.; Lightcap, E.S.; Koo, Y.K.; Lu, X.; Quancard, J.; Silverman, R.B.Purification and inactivation of 3-hydroxyanthranilic acid 3,4-dioxygenase from beef liverInt. J. Biochem. Cell Biol.351085-10972003Bos taurus PubMed
672036Colabroy, K.L.; Zhai, H.; Li, T.; Ge, Y.; Zhang, Y.; Liu, A.; Ealick, S.E.; McLafferty, F.W.; Begley, T.P.The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilateBiochemistry447623-76312005Cupriavidus metallidurans PubMed
672037Zhang, Y.; Colabroy, K.L.; Begley, T.P.; Ealick, S.E.Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic mechanism of a complex oxidation involved in NAD biosynthesisBiochemistry447632-76432005Cupriavidus metallidurans PubMed
673130Comai, S.; Costa, C.V.; Ragazzi, E.; Bertazzo, A.; Allegri, G.The effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway in ratsClin. Chim. Acta36067-802005Rattus norvegicus PubMed
675557Yates Jennifer , Y.J.; Heyes Melvyn , H.M.; Blight Andrew , B.A.4-chloro-3-hydroxyanthranilate reduces local quinolinic acid synthesis, improves functional recovery, and preserves white matter after spinal cord injuryJ. Neurotrauma23866-8812006Cavia porcellus PubMed
675782Maharaj, H.; Maharaj, D.S.; Daya, S.Acetylsalicylic acid and acetaminophen protect against oxidative neurotoxicityMetab. Brain Dis.21189-1992006Rattus norvegicus PubMed
677020Li, X.; Guo, M.; Fan, J.; Tang, W.; Wang, D.; Ge, H.; Rong, H.; Teng, M.; Niu, L.; Liu, Q.; Hao, Q.Crystal structure of 3-hydroxyanthranilic acid 3,4-dioxygenase from Saccharomyces cerevisiae: a special subgroup of the type III extradiol dioxygenasesProtein Sci.15761-7732006Saccharomyces cerevisiae PubMed
696784Dilovic, I.; Gliubich, F.; Malpeli, G.; Zanotti, G.; Matkovic-Calogovic, D.Crystal structure of bovine 3-hydroxyanthranilate 3,4-dioxygenaseBiopolymers911189-11952009Bos taurus PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 1.13.11.6)
ExplorEnz
ExPASy
KEGG
MetaCyc
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
SYSTERS
Protein Mutant Database
InterPro (database of protein families, domains and functional sites)