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6kof

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Current revision

Crystal structure of indoleamine 2,3-dioxygenagse 1 (IDO1) in complex with compound 47

Structural highlights

6kof is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.263Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 (IDO1) inhibitors are speculated to be useful in cancer immunotherapy, but a phase III clinical trial of the most advanced IDO1 inhibitor, epacadostat, did not meet its primary end point and was abandoned. In previous work, we identified the novel IDO1 inhibitor N-(4-chlorophenyl)-2-((5-phenylthiazolo[2,3-c][1,2,4]triazol-3-yl)thio)acetamide 1 through high-throughput screening (HTS). Herein, we report a structure-activity relationship (SAR) study of this compound, which resulted in the potent IDO1 inhibitor 1-(4-cyanophenyl)-3-(3-(cyclopropylethynyl)imidazo[2,1-b]thiazol-5-yl)thiourea 47 (hIDO IC50 = 16.4 nM). X-ray cocrystal structural analysis revealed that the basis for this high potency is a unique sulfur-aromatic interaction network formed by the thiourea moiety of 47 with F163 and F226. This finding is expected to inspire new approaches toward the discovery of potent IDO1 inhibitors in the future.

Unique Sulfur-Aromatic Interactions Contribute to the Binding of Potent Imidazothiazole Indoleamine 2,3-Dioxygenase Inhibitors.,Peng YH, Liao FY, Tseng CT, Kuppusamy R, Li AS, Chen CH, Fan YS, Wang SY, Wu MH, Hsueh CC, Chang JY, Lee LC, Shih C, Shia KS, Yeh TK, Hung MS, Kuo CC, Song JS, Wu SY, Ueng SH J Med Chem. 2020 Feb 27;63(4):1642-1659. doi: 10.1021/acs.jmedchem.9b01549. Epub , 2020 Feb 10. PMID:31961685^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Peng YH, Liao FY, Tseng CT, Kuppusamy R, Li AS, Chen CH, Fan YS, Wang SY, Wu MH, Hsueh CC, Chang JY, Lee LC, Shih C, Shia KS, Yeh TK, Hung MS, Kuo CC, Song JS, Wu SY, Ueng SH. Unique Sulfur-Aromatic Interactions Contribute to the Binding of Potent Imidazothiazole Indoleamine 2,3-Dioxygenase Inhibitors. J Med Chem. 2020 Feb 27;63(4):1642-1659. doi: 10.1021/acs.jmedchem.9b01549. Epub , 2020 Feb 10. PMID:31961685 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01549

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6kof"

Categories: Homo sapiens | Large Structures | Peng YH | Wu SY

@@ Line 3: / Line 3: @@
 <StructureSection load='6kof' size='340' side='right'caption='[[6kof]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kof]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KOF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KOF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kof]] 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=6KOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KOF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DO9:1-(4-cyanophenyl)-3-[[3-(2-cyclopropylethynyl)imidazo[2,1-b][1,3]thiazol-5-yl]methyl]thiourea'>DO9</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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]] 2.263&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DO9:1-(4-cyanophenyl)-3-[[3-(2-cyclopropylethynyl)imidazo[2,1-b][1,3]thiazol-5-yl]methyl]thiourea'>DO9</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></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=6kof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kof OCA], [http://pdbe.org/6kof PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kof RCSB], [http://www.ebi.ac.uk/pdbsum/6kof PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kof 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=6kof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kof OCA], [https://pdbe.org/6kof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kof RCSB], [https://www.ebi.ac.uk/pdbsum/6kof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kof ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6kof" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Indoleamine 2,3-dioxygenase]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Peng, Y H]]
+[[Category: Peng YH]]
-[[Category: Wu, S Y]]
+[[Category: Wu SY]]
-[[Category: Heme]]
-[[Category: Immunity]]
-[[Category: Iron]]
-[[Category: Kynurenine]]
-[[Category: Metal binding]]
-[[Category: Oxidoreductase-inhibitor complex]]
-[[Category: Tryptophan catabolism]]

6kof

From Proteopedia

Current revision

Crystal structure of indoleamine 2,3-dioxygenagse 1 (IDO1) in complex with compound 47

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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