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| | <StructureSection load='5tkq' size='340' side='right'caption='[[5tkq]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='5tkq' size='340' side='right'caption='[[5tkq]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tkq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tkq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TKQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HAAO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-hydroxyanthranilate_3,4-dioxygenase 3-hydroxyanthranilate 3,4-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.6 1.13.11.6] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkq OCA], [https://pdbe.org/5tkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tkq RCSB], [https://www.ebi.ac.uk/pdbsum/5tkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkq ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkq OCA], [http://pdbe.org/5tkq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tkq RCSB], [http://www.ebi.ac.uk/pdbsum/5tkq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/3HAO_HUMAN 3HAO_HUMAN]] Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.<ref>PMID:7514594</ref> | + | [https://www.uniprot.org/uniprot/3HAO_HUMAN 3HAO_HUMAN] Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.<ref>PMID:7514594</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-hydroxyanthranilate 3,4-dioxygenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pidugu, L S]] | + | [[Category: Pidugu LS]] |
| - | [[Category: Toth, E A]] | + | [[Category: Toth EA]] |
| - | [[Category: 3-hydroxyanthranilate oxygenase]]
| + | |
| - | [[Category: Cupin kynurenine pathway]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
3HAO_HUMAN Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.[1]
Publication Abstract from PubMed
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.
Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.,Pidugu LS, Neu H, Wong TL, Pozharski E, Molloy JL, Michel SL, Toth EA Acta Crystallogr D Struct Biol. 2017 Apr 1;73(Pt 4):340-348. doi:, 10.1107/S2059798317002029. Epub 2017 Mar 31. PMID:28375145[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Malherbe P, Kohler C, Da Prada M, Lang G, Kiefer V, Schwarcz R, Lahm HW, Cesura AM. Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. J Biol Chem. 1994 May 13;269(19):13792-7. PMID:7514594
- ↑ Pidugu LS, Neu H, Wong TL, Pozharski E, Molloy JL, Michel SL, Toth EA. 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. 2017 Apr 1;73(Pt 4):340-348. doi:, 10.1107/S2059798317002029. Epub 2017 Mar 31. PMID:28375145 doi:http://dx.doi.org/10.1107/S2059798317002029
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