PDBsum entry 5tk5

Oxidoreductase

PDB id: 5tk5

Contents

Protein chain

283 a.a.

Ligands

SO4 ×3

Metals

_FE

Waters ×173

PDB id:

5tk5

Name:

Oxidoreductase

Title:

Crystal structure of human 3hao with iron bound in the active site

Structure:

3-hydroxyanthranilate 3,4-dioxygenase. Chain: a. Synonym: 3-hydroxyanthranilate oxygenase,3-hao,3-hydroxyanthranilic acid dioxygenase,had. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: haao. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.88Å R-factor: 0.203 R-free: 0.218

Authors:

L.S.Pidugu,E.A.Toth

Key ref:

L.S.Pidugu et al. (2017). Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. Acta Crystallogr D Struct Biol, 73, 340-348. PubMed id: 28375145 DOI: 10.1107/S2059798317002029

Date:

06-Oct-16 Release date: 12-Apr-17

Protein chain

P46952  (3HAO_HUMAN) -  3-hydroxyanthranilate 3,4-dioxygenase from Homo sapiens

Seq: 286 a.a.

Struc: 283 a.a.

Enzyme reactions

• Enzyme class: E.C.1.13.11.6 - 3-hydroxyanthranilate 3,4-dioxygenase.
• Pathway: (later stages)
• Reaction: 3-hydroxyanthranilate + O2 = (2Z,4Z)-2-amino-3-carboxymuconate 6-semialdehyde
• Cofactor: Fe cation

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1107/S2059798317002029

Acta Crystallogr D Struct Biol 73:340-348 (2017)

PubMed id: 28375145

Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.

L.S.Pidugu, H.Neu, T.L.Wong, E.Pozharski, J.L.Molloy, S.L.Michel, E.A.Toth.

ABSTRACT

3-Hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation. 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 (QUIN). QUIN is a highly potent excitotoxin that has been implicated in a number of neurodegenerative conditions, making 3HAO a target for pharmacological downregulation. Here, the first crystal structure of human 3HAO with the native iron bound in its active site is presented, together with an additional structure with zinc (a known inhibitor of human 3HAO) bound in the active site. The metal-binding environment is examined both structurally and via inductively coupled plasma mass spectrometry (ICP-MS), X-ray fluorescence spectroscopy (XRF) and electron paramagnetic resonance spectroscopy (EPR). The studies identified Met35 as the source of potential new interactions with substrates and inhibitors, which may prove useful in future therapeutic efforts.