7zv3: Difference between revisions
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<table><tr><td colspan='2'>[[7zv3]] 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=7ZV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZV3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zv3]] 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=7ZV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZV3 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]] 2.551Å</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]] 2.551Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=RCT: | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=RCT:5-[3-chloranyl-2-(2-phenylethyl)phenyl]-1~{H}-1,2,3-triazole'>RCT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7zv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zv3 OCA], [https://pdbe.org/7zv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zv3 RCSB], [https://www.ebi.ac.uk/pdbsum/7zv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zv3 ProSAT]</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=7zv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zv3 OCA], [https://pdbe.org/7zv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zv3 RCSB], [https://www.ebi.ac.uk/pdbsum/7zv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zv3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | [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 == | |||
The haem enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the rate-limiting step in the kynurenine pathway of tryptophan metabolism and plays an essential role in immunity, neuronal function, and ageing. Expression of IDO1 in cancer cells results in the suppression of an immune response, and therefore IDO1 inhibitors have been developed for use in anti-cancer immunotherapy. Here, we report an extension of our previously described highly efficient haem-binding 1,2,3-triazole and 1,2,4-triazole inhibitor series, the best compound having both enzymatic and cellular IC(50) values of 34 nM. We provide enzymatic inhibition data for almost 100 new compounds and X-ray diffraction data for one compound in complex with IDO1. Structural and computational studies explain the dramatic drop in activity upon extension to pocket B, which has been observed in diverse haem-binding inhibitor scaffolds. Our data provides important insights for future IDO1 inhibitor design. | |||
Structure-based optimization of type III indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.,Rohrig UF, Majjigapu SR, Vogel P, Reynaud A, Pojer F, Dilek N, Reichenbach P, Ascencao K, Irving M, Coukos G, Michielin O, Zoete V J Enzyme Inhib Med Chem. 2022 Dec;37(1):1773-1811. doi: , 10.1080/14756366.2022.2089665. PMID:35758198<ref>PMID:35758198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7zv3" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Latest revision as of 14:51, 23 October 2024
Crystal structure of indoleamine 2,3-dioxygenase 1 (IDO1) in complex with ferric heme and MMG-0472Crystal structure of indoleamine 2,3-dioxygenase 1 (IDO1) in complex with ferric heme and MMG-0472
Structural highlights
FunctionI23O1_HUMAN Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.[1] Publication Abstract from PubMedThe haem enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the rate-limiting step in the kynurenine pathway of tryptophan metabolism and plays an essential role in immunity, neuronal function, and ageing. Expression of IDO1 in cancer cells results in the suppression of an immune response, and therefore IDO1 inhibitors have been developed for use in anti-cancer immunotherapy. Here, we report an extension of our previously described highly efficient haem-binding 1,2,3-triazole and 1,2,4-triazole inhibitor series, the best compound having both enzymatic and cellular IC(50) values of 34 nM. We provide enzymatic inhibition data for almost 100 new compounds and X-ray diffraction data for one compound in complex with IDO1. Structural and computational studies explain the dramatic drop in activity upon extension to pocket B, which has been observed in diverse haem-binding inhibitor scaffolds. Our data provides important insights for future IDO1 inhibitor design. Structure-based optimization of type III indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.,Rohrig UF, Majjigapu SR, Vogel P, Reynaud A, Pojer F, Dilek N, Reichenbach P, Ascencao K, Irving M, Coukos G, Michielin O, Zoete V J Enzyme Inhib Med Chem. 2022 Dec;37(1):1773-1811. doi: , 10.1080/14756366.2022.2089665. PMID:35758198[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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