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 .
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 |