View source for 6r63


==Crystal structure of indoleamine 2,3-dioxygenase 1 (IDO1) in complex with ferric heme and MMG-0358==
<StructureSection load='6r63' size='340' side='right'caption='[[6r63]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.894&#8491;</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='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>
</table>
== Function ==
[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;">
== 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<ref>PMID:31525930</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6r63" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Michielin O]]
[[Category: Pojer F]]
[[Category: Reynaud A]]
[[Category: Roehrig UF]]
[[Category: Zoete V]]