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| | <StructureSection load='6r63' size='340' side='right'caption='[[6r63]], [[Resolution|resolution]] 2.89Å' scene=''> | | <StructureSection load='6r63' size='340' side='right'caption='[[6r63]], [[Resolution|resolution]] 2.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6r63]] is a 2 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=6R63 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R63 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6r63]] is a 2 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=6R63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R63 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=JTB:4-chloranyl-2-(2~{H}-1,2,3-triazol-4-yl)phenol'>JTB</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]] 2.894Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IDO1, IDO, INDO ([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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=JTB:4-chloranyl-2-(2~{H}-1,2,3-triazol-4-yl)phenol'>JTB</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase Indoleamine 2,3-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.52 1.13.11.52] </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=6r63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r63 OCA], [https://pdbe.org/6r63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r63 RCSB], [https://www.ebi.ac.uk/pdbsum/6r63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r63 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=6r63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r63 OCA], [http://pdbe.org/6r63 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r63 RCSB], [http://www.ebi.ac.uk/pdbsum/6r63 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r63 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6r63" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6r63" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Indoleamine 2,3-dioxygenase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Michielin, O]] | + | [[Category: Michielin O]] |
| - | [[Category: Pojer, F]] | + | [[Category: Pojer F]] |
| - | [[Category: Reynaud, A]] | + | [[Category: Reynaud A]] |
| - | [[Category: Roehrig, U F]] | + | [[Category: Roehrig UF]] |
| - | [[Category: Zoete, V]] | + | [[Category: Zoete V]] |
| - | [[Category: Dioxygenase]]
| + | |
| - | [[Category: Heme-containing enzyme]]
| + | |
| - | [[Category: Ido1 inhibitor]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Small-molecule inhibitor]]
| + | |
| - | [[Category: Structure-based drug design]]
| + | |
| - | [[Category: Triazole]]
| + | |
| Structural highlights
Function
I23O1_HUMAN Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.[1]
Publication Abstract from PubMed
Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative diseases has stimulated the development of IDO1 inhibitors. However, negative phase III clinical trial results of the IDO1 inhibitor epacadostat in cancer immunotherapy call for a better understanding of the role and the mechanisms of IDO1 inhibition. In this work, we investigate the molecular inhibition mechanisms of four known IDO1 inhibitors and of two quinones in detail, using different experimental and computational approaches. We also determine for the first time the X-ray structure of the highly efficient 1,2,3-triazole inhibitor MMG-0358. Based on our results and a comprehensive literature overview, we propose a classification scheme for IDO1 inhibitors according to their inhibition mechanism, which will be useful for further developments in the field.
Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1).,Rohrig UF, Reynaud A, Majjigapu SR, Vogel P, Pojer F, Zoete V J Med Chem. 2019 Sep 26. doi: 10.1021/acs.jmedchem.9b00942. PMID:31525930[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res. 2007 Aug 1;67(15):7082-7. PMID:17671174 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-1872
- ↑ Rohrig UF, Reynaud A, Majjigapu SR, Vogel P, Pojer F, Zoete V. Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1). J Med Chem. 2019 Sep 26. doi: 10.1021/acs.jmedchem.9b00942. PMID:31525930 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00942
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