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Information on EC 1.13.11.6 - 3-hydroxyanthranilate 3,4-dioxygenase and Organism(s) Homo sapiens
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1.13.11.6 3-hydroxyanthranilate 3,4-dioxygenaseIUBMB Comments
Requires Fe2+.
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Word Map
- 1.13.11.6
-
quinolinic
- kynureninase
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quin
-
2,3-dioxygenase
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3-monooxygenase
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excitotoxin
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phosphoribosyltransferase
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kynurenine-oxoglutarate
- aminocarboxymuconate-semialdehyde
-
kynurenic
- 3-hydroxykynurenine
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ibotenic
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epilepsy-prone
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picolinic
- drug development
- medicine
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
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
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-hydroxyanthranilate oxygenase
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3-hydroxyanthranilic acid oxidase
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3-hydroxyanthranilic acid oxygenase
3-hydroxyanthranilic oxygenase
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3HAO
oxygenase, 3-hydroxyanthranilate 3,4-di-
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3-hydroxyanthranilic acid oxygenase
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3HAO
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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SYSTEMATIC NAME
IUBMB Comments
3-hydroxyanthranilate:oxygen 3,4-oxidoreductase (decyclizing)
Requires Fe2+.
CAS REGISTRY NUMBER
COMMENTARY
9029-50-9
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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
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
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-
-
r
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
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-
-
?
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
3-hydroxyanthranilate + O2
2-amino-3-carboxymuconate semialdehyde
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-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
additional information
additional information
comparison of the active sites of Fe(III)-h3HAO and Zn(II)-h3HAO enzymes, overview
additional information
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comparison of the active sites of Fe(III)-h3HAO and Zn(II)-h3HAO enzymes, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
3-hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation
physiological function
additional information
physiological function
enzyme 3HAO is a non-heme iron-containing, ring-cleaving extradiol dioxygenase that catalyzes the addition of both atoms of O2 to the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3-HANA) to form quinolinic acid. Quinolinic acid is a highly potent excitotoxin that is implicated in a number of neurodegenerative conditions
physiological function
the enzyme catalyses the cleavage of the benzene ring of 3-hydroxyanthranilic acid (3-Ohaa), an intermediate in the kynurenine pathway
additional information
enzyme molecular modeling, the water population of the active site, and the protein flexibility as well as the amino acid residues interaction networks are relevant for the enzyme activity, hybrid quantum-mechanics/molecular-mechanics (QM/MM) calculations
additional information
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enzyme molecular modeling, the water population of the active site, and the protein flexibility as well as the amino acid residues interaction networks are relevant for the enzyme activity, hybrid quantum-mechanics/molecular-mechanics (QM/MM) calculations
additional information
residue Met35 is involved in interactions with substrates and inhibitors
additional information
-
residue Met35 is involved in interactions with substrates and inhibitors
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). 3HAO_HUMAN
286
0
32556
Swiss-Prot
Mitochondrion (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant detagged enzyme in complex with Zn2+ or Fe2+, protein with zinc sulfate or iron sulfate best from 0.1 M HEPES, pH 7.5, 2% PEG 400, and 2.0 M ammonium sulfate., in 2-7 days, X-ray diffraction structure determination and analysis at 1.75-1.88 A resolution, modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q105A
site-directed mutagenesis, the mutation affects the enzyme activity, the protein structure, particularly the active site architecture and the metal ion environment, and the substrate binding
R43A
site-directed mutagenesis, the mutation affects the enzyme activity, the protein structure, particularly the active site architecture and the metal ion environment, and the substrate binding
R95A
site-directed mutagenesis, the mutation affects the enzyme activity, the protein structure, particularly the active site architecture and the metal ion environment, and the substrate binding
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-MBP-tagged enzyme from Escherichia coli by nickel affinity chromatography and cleavage of the His-tag by TEV protease, elimination of the tags by nickel affinity and amylose affinity chromatography, te final step is gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
pharmacology
the enzyme is a target for pharmacological downregulation because it is involved in formation of quinolinic acid, a highly potent excitotoxin implicated in a number of neurodegenerative conditions
drug development
the enzyme is a a potential target in treating numerous disorders related to the concentration of quinolinic acid, the kynurenine pathway product
drug development
the enzyme is a target for pharmacological downregulation because it is involved in formation of quinolinic acid, a highly potent excitotoxin implicated in a number of neurodegenerative conditions
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Calderone, 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. Acta
1596
283-292
2002
Homo sapiens
Pidugu, L.S.; Neu, H.; Wong, T.L.; Pozharski, E.; Molloy, J.L.; Michel, S.L.; Toth, E.A.
Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site
Acta Crystallogr. Sect. D
73
340-348
2017
Homo sapiens (P46952), Homo sapiens
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