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| ==Crystal structure of IDO1 in complex with Apoxidole-1== | | ==Crystal structure of IDO1 in complex with Apoxidole-1== |
| <StructureSection load='8abx' size='340' side='right'caption='[[8abx]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='8abx' size='340' side='right'caption='[[8abx]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[8abx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ABX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ABX FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ABX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ABX FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N2U:O2-tert-butyl+O3-ethyl+O6-methyl+(2S,6R)-6-(1-methylindol-2-yl)-2,5-dihydro-1H-pyridine-2,3,6-tricarboxylate'>N2U</scene>, <scene name='pdbligand=N39:O1-tert-butyl+O2-ethyl+O5-methyl+(E,5R)-5-(1-methylindol-2-yl)-5-[(4-methylphenyl)sulfonylamino]pent-2-ene-1,2,5-tricarboxylate'>N39</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | | </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=8abx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8abx OCA], [https://pdbe.org/8abx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8abx RCSB], [https://www.ebi.ac.uk/pdbsum/8abx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8abx ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase Indoleamine 2,3-dioxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.52 1.13.11.52] </span></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8abx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8abx OCA], [https://pdbe.org/8abx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8abx RCSB], [https://www.ebi.ac.uk/pdbsum/8abx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8abx ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[https://www.uniprot.org/uniprot/I23O1_HUMAN I23O1_HUMAN]] Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.<ref>PMID:17671174</ref>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo-NP class, whereby indole- and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo-IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo-IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research.
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| Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype.,Davies C, Dotsch L, Ciulla MG, Hennes E, Yoshida K, Gasper R, Scheel R, Sievers S, Strohmann C, Kumar K, Ziegler S, Waldmann H Angew Chem Int Ed Engl. 2022 Aug 12:e202209374. doi: 10.1002/anie.202209374. PMID:35959923<ref>PMID:35959923</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 8abx" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Indoleamine 2,3-dioxygenase]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Dotsch, L]] | | [[Category: Dotsch L]] |
| [[Category: Gasper, R]] | | [[Category: Gasper R]] |
| [[Category: Waldmann, H]] | | [[Category: Waldmann H]] |
| [[Category: Ziegler, S]] | | [[Category: Ziegler S]] |
| [[Category: 3-dioxygenase 1]]
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| [[Category: Heme-binding protein]]
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| [[Category: Indoleamine 2]]
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| [[Category: Natural product]]
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| [[Category: Oxidoreductase]]
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