5TK5
Crystal structure of human 3HAO with iron bound in the active site
Summary for 5TK5
| Entry DOI | 10.2210/pdb5tk5/pdb |
| Descriptor | 3-hydroxyanthranilate 3,4-dioxygenase, FE (III) ION, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | 3-hydroxyanthranilate oxygenase dioxygenase, cupin kynurenine pathway, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 33236.41 |
| Authors | Pidugu, L.S.,Toth, E.A. (deposition date: 2016-10-06, release date: 2017-04-12, Last modification date: 2023-10-04) |
| Primary citation | 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 D Struct Biol, 73:340-348, 2017 Cited by PubMed 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 O 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. PubMed: 28375145DOI: 10.1107/S2059798317002029 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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