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Literature summary extracted from

  • 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 (2017), Acta Crystallogr. Sect. D, 73, 340-348 .
    View publication on PubMed

Application

EC Number Application Comment Organism
1.13.11.6 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 Homo sapiens
1.13.11.6 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 Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.13.11.6 recombinant expression of His6-MBP-tagged enzyme in Escherichia coli Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.13.11.6 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 Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.13.11.6 Zn2+ binds at the active site, binding structure, overview Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.13.11.6 Fe2+ a non-heme iron-containing enzyme, binding structure, overview Homo sapiens
1.13.11.6 additional information comparison of the active sites of Fe(III)-h3HAO and Zn(II)-h3HAO enzymes, overview Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.13.11.6 3-hydroxyanthranilate + O2 Homo sapiens
-
2-amino-3-carboxymuconate semialdehyde
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.13.11.6 Homo sapiens P46952
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.13.11.6 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 Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
1.13.11.6 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 Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.13.11.6 3-hydroxyanthranilate + O2
-
Homo sapiens 2-amino-3-carboxymuconate semialdehyde
-
?

Synonyms

EC Number Synonyms Comment Organism
1.13.11.6 3-hydroxyanthranilic acid oxygenase
-
Homo sapiens
1.13.11.6 3HAO
-
Homo sapiens

General Information

EC Number General Information Comment Organism
1.13.11.6 metabolism 3-hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation Homo sapiens
1.13.11.6 additional information residue Met35 is involved in interactions with substrates and inhibitors Homo sapiens
1.13.11.6 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 Homo sapiens