Any feedback?
Information on EC 1.13.11.6 - 3-hydroxyanthranilate 3,4-dioxygenase
for references in articles please use BRENDA:EC1.13.11.6Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.13.11.6 3-hydroxyanthranilate 3,4-dioxygenaseIUBMB Comments
Requires Fe2+.
Specify your search results
Word Map
- 1.13.11.6
-
quinolinic
- kynureninase
-
quin
-
2,3-dioxygenase
-
3-monooxygenase
-
excitotoxin
-
phosphoribosyltransferase
-
kynurenine-oxoglutarate
- aminocarboxymuconate-semialdehyde
-
kynurenic
- 3-hydroxykynurenine
-
ibotenic
-
epilepsy-prone
-
picolinic
- drug development
- medicine
- pharmacology
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
3-hydroxyanthranilate 3,4-dioxygenase, 3-hydroxyanthranilic acid oxygenase, 3-hao, 3-hydroxyanthranilate oxygenase, 3-had, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-HAD
3-HAO
3-hydroxyanthranilate 3,4-dioxygenase
3-hydroxyanthranilate oxygenase
-
-
-
-
3-hydroxyanthranilic acid oxidase
-
-
-
-
3-hydroxyanthranilic acid oxygenase
3-hydroxyanthranilic oxygenase
-
-
-
-
3HAO
EC 1.13.1.6
-
-
formerly
-
HAO
oxygenase, 3-hydroxyanthranilate 3,4-di-
-
-
-
-
3-hydroxyanthranilic acid oxygenase
-
-
-
-
3HAO
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-hydroxyanthranilate + O2 = 2-amino-3-carboxymuconate semialdehyde
reaction mechanism, overview
-
3-hydroxyanthranilate + O2 = 2-amino-3-carboxymuconate semialdehyde
the 3HAO reaction is initiated by substrate binding, which induces closure of the active site. Oxygen then binds to the active-site iron. Transfer of an electron from the active-site iron to oxygen creates an oxygen radical, thereby facilitating the addition of both O atoms to 3-HANA and forming 2-amino-3-carboxymuconic 6-semialdehyde (ACMS), an active intermediate. ACMS then spontaneously cyclizes to form quinolinic acid
3-hydroxyanthranilate + O2 = 2-amino-3-carboxymuconate semialdehyde
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
3-hydroxyanthranilate:oxygen 3,4-oxidoreductase (decyclizing)
Requires Fe2+.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
9029-50-9
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-amino-3-hydroxybenzoic acid + O2
2,3-pyridinedicarboxylic acid + H2O
-
intermediate 2-amino-3-carboxymuconic acid semialdehyde
-
?
4-ethyl-3-hydroxyanthranilate + O2
2-amino-3-carboxy-4-ethylmuconate semialdehyde
-
-
-
?
4-methyl-3-hydroxyanthranilate + O2
2-amino-3-carboxy-4-methylmuconate semialdehyde
-
-
-
?
4-propyl-3-hydroxyanthranilic acid + O2
2-amino-3-carboxy-4-propylmuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
the enzymatic product subsequently cyclizes to quinolinate
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
the enzyme employs loop dynamics to accommodate two substrates with disparate polarities
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
the enzyme employs loop dynamics to accommodate two substrates with disparate polarities
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
r
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
enzyme occurs in the metabolic pathway of the conversion of tryptophan to nicotinic acid
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
high selectivity for substrate
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
in mammalian peripheral organs the enzyme constitutes a link in the catabolic pathway of tryptophan to NAD+
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
biosynthetic enzyme of the endogenous excitotoxin quinolinic acid
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
reacts spontaneously to quinolinic acid
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
in the kynurenine pathway
-
-
?
additional information
?
-
no 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 substrates
-
-
?
additional information
?
-
-
no 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 substrates
-
-
?
additional information
?
-
no 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 substrates
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-amino-3-hydroxybenzoic acid + O2
2,3-pyridinedicarboxylic acid + H2O
-
intermediate 2-amino-3-carboxymuconic acid semialdehyde
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
enzyme occurs in the metabolic pathway of the conversion of tryptophan to nicotinic acid
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
-
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
in mammalian peripheral organs the enzyme constitutes a link in the catabolic pathway of tryptophan to NAD+
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
biosynthetic enzyme of the endogenous excitotoxin quinolinic acid
-
-
?
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
-
in the kynurenine pathway
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe
-
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 A
Fe2+
Iron
Ni2+
-
two nickel binding sites per molecule. One of the bound nickel atoms occupies the proposed ferrous-coordinated active site
additional information
Fe2+
-
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 form
Fe2+
-
required, the active site of HAD contains an iron(II) center that is coordinated by the 2-His-1-Glu facial triad
Iron
enhanced hydrophobicity at the iron center results from the concerted loop movements after the binding of the primary substrate
additional information
comparison of the active sites of Fe(III)-h3HAO and Zn(II)-h3HAO enzymes, overview
additional information
-
comparison of the active sites of Fe(III)-h3HAO and Zn(II)-h3HAO enzymes, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide methiodide
carboxyl-directed reagent, 1 mM, 26% inhibition
4,6-dibromo-3-hydroxyanthranilic acid
-
NCR-631, characterization of in vivo effects, reversible inhibition with short half-life following systematic administration
6-chloro-3-hydroxyanthranilic acid
-
5-20 mM, loss of enzymatic activity as a function of the inhibitor concentration
diethyl dicarbonate
modifies histidine residues of catechol dioxygenases, 1 mM, 70% inhibition
Dithionitrobenzoic acid
cysteine-directed reagent, 1 mM, complete inhibition
o-methoxybenzoylalanine
-
in whole-liver homogenates, but in purified enzyme preparations only in the presence of mitochondria
4-Chloro-3-hydroxyanthranilate
-
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 neurotoxicity
4-Chloro-3-hydroxyanthranilate
-
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 site
additional information
-
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 acid
-
additional information
-
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 potency
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Carcinoma, Hepatocellular
Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase.
Glioma
The endogenous tryptophan metabolite and NAD+ precursor quinolinic acid confers resistance of gliomas to oxidative stress.
Huntington Disease
3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims.
Hyperglycemia
Changes in mouse liver and chicken embryo yolk sac membrane soluble proteins due to an organophosphorous insecticide (OPI) diazinon linked to several noncholinergic OPI effects in mice and chicken embryos.
Infections
Antiviral Effect of IDO in Mouse Fibroblast Cells During Influenza Virus Infection.
Neurodegenerative Diseases
2-Aminonicotinic acid 1-oxides are chemically stable inhibitors of quinolinic acid synthesis in the mammalian brain: a step toward new antiexcitotoxic agents.
Olivopontocerebellar Atrophies
Quinolinic acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy.
Seizures
Anticonvulsant effects of the 3-hydroxyanthranilic acid dioxygenase inhibitor NCR-631.
Seizures
Differential expression of the astrocytic enzymes 3-hydroxyanthranilic acid oxygenase, kynurenine aminotransferase and glutamine synthetase in seizure-prone and non-epileptic mice.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
comparison of values of wild-type and deleted complemented strains
additional information
comparison of values of wild-type and deleted complemented strains
additional information
-
comparison of values of wild-type and deleted complemented strains
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 7
-
at pH 4.5: about 70% of activity maximum, at pH 7.0: about 50% of activity maximum
additional information
-
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 enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0 - 50
-
enzyme activity increased almost linearly with temperature, beyond a sharp drop
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
