5xe1

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the indoleamine 2,3-dioxygenagse 1 (IDO1) complexed with INCB14943

Structural highlights

5xe1 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 3.2Å
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

IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive enzyme, has attracted growing attention as a potential target for cancer immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360 analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical trials for treatment of various types of human cancer. Here, we determined the co-crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode. INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen. Further analysis also reveals that a halogen bonding interaction between the chlorine atom (3-Cl) of INCB14943 and the sulphur atom of C129 significantly improves the inhibition activity against IDO1. Comparing with the other reported inhibitors, the oxime nitrogen and halogen bond interaction are identified as the unique features of INCB14943 among the IDO1 inhibitors. Thus, our study provides novel insights into the interaction between a small molecule inhibitor INCB14943 and IDO1 protein. The structural information will facilitate future IDO1 inhibitor design.

Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943.,Wu Y, Xu T, Liu J, Ding K, Xu J Biochem Biophys Res Commun. 2017 May 27;487(2):339-343. doi:, 10.1016/j.bbrc.2017.04.061. Epub 2017 Apr 13. PMID:28412361^[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
↑ Wu Y, Xu T, Liu J, Ding K, Xu J. Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943. Biochem Biophys Res Commun. 2017 May 27;487(2):339-343. doi:, 10.1016/j.bbrc.2017.04.061. Epub 2017 Apr 13. PMID:28412361 doi:http://dx.doi.org/10.1016/j.bbrc.2017.04.061

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/5xe1"

Categories: Homo sapiens | Large Structures | Liu J | Wu U | Xu J

@@ Line 1: / Line 1: @@
 ==Crystal structure of the indoleamine 2,3-dioxygenagse 1 (IDO1) complexed with INCB14943==
-<StructureSection load='5xe1' size='340' side='right' caption='[[5xe1]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='5xe1' size='340' side='right'caption='[[5xe1]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xe1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XE1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xe1]] 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=5XE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XE1 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=IUU:4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXAMIDINE'>IUU</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]] 3.2&#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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IUU:4-AMINO-N-(3-CHLORO-4-FLUOROPHENYL)-N-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXAMIDINE'>IUU</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=5xe1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xe1 OCA], [http://pdbe.org/5xe1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xe1 RCSB], [http://www.ebi.ac.uk/pdbsum/5xe1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xe1 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=5xe1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xe1 OCA], [https://pdbe.org/5xe1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xe1 RCSB], [https://www.ebi.ac.uk/pdbsum/5xe1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xe1 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 5xe1" 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: Liu, J]]
+[[Category: Large Structures]]
-[[Category: Wu, U]]
+[[Category: Liu J]]
-[[Category: Xu, J]]
+[[Category: Wu U]]
-[[Category: Ido1]]
+[[Category: Xu J]]
-[[Category: Incb14943]]
-[[Category: Oxidoreductase]]

5xe1

From Proteopedia

Current revision

Crystal structure of the indoleamine 2,3-dioxygenagse 1 (IDO1) complexed with INCB14943

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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