Literature summary for 1.13.11.6 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 .

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Application

Application	Comment	Organism
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
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)

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

Crystallization (Commentary)

Crystallization (Comment)	Organism
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

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

Metals/Ions

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P46952	-	-

Purification (Commentary)

Purification (Comment)	Organism
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

Reaction	Comment	Organism	Reaction ID
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	a

Substrates and Products (Substrate)

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

Synonyms

Synonyms	Comment	Organism
3-hydroxyanthranilic acid oxygenase	-	Homo sapiens
3HAO	-	Homo sapiens

General Information

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

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Release 2023.1 (January 2023)