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==CRYSTAL STRUCTURE OF HUMAN INDOLEAMINE 2,3-DIOXYGENASE 1 (IDO1) in complex with ferric heme and an Epacadostat analog== | |||
<StructureSection load='6e41' size='340' side='right' caption='[[6e41]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6e41]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E41 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=HQS:N-(3-bromo-4-fluorophenyl)-N-hydroxy-4-{[2-(sulfamoylamino)ethyl]sulfanyl}-1,2,5-oxadiazole-3-carboximidamide'>HQS</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e41 OCA], [http://pdbe.org/6e41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e41 RCSB], [http://www.ebi.ac.uk/pdbsum/6e41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e41 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-dependent enzyme with important roles in many cellular processes and is a potential target for drug discovery against cancer and other diseases. Crystal structures of IDO1 in complex with various inhibitors have been reported. Many of these crystals belong to the same crystal form and most of the reported structures have resolutions in the range 3.2-2.3 A. Here, three new crystal forms of human IDO1 obtained by introducing a surface mutation, K116A/K117A, distant from the active site are reported. One of these crystal forms diffracted to 1.5 A resolution and can be readily used for soaking experiments to determine high-resolution structures of IDO1 in complex with the substrate tryptophan or inhibitors that coordinate the heme. In addition, this mutant was used to produce crystals of a complex with an inhibitor that targets the apo form of the enzyme under the same conditions; the structure of this complex was determined at 1.7 A resolution. Overall, this mutant represents a robust platform for determining the structures of inhibitor and substrate complexes of IDO1 at high resolution. | |||
High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form.,Luo S, Xu K, Xiang S, Chen J, Chen C, Guo C, Tong Y, Tong L Acta Crystallogr F Struct Biol Commun. 2018 Nov 1;74(Pt 11):717-724. doi:, 10.1107/S2053230X18012955. Epub 2018 Oct 17. PMID:30387777<ref>PMID:30387777</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6e41" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Indoleamine 2,3-dioxygenase]] | |||
[[Category: Luo, S]] | |||
[[Category: Tong, L]] | |||
[[Category: Epacadostat analog]] | |||
[[Category: Ido1]] | |||
[[Category: Inhibitor complex]] | |||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | |||
Revision as of 11:16, 14 November 2018
CRYSTAL STRUCTURE OF HUMAN INDOLEAMINE 2,3-DIOXYGENASE 1 (IDO1) in complex with ferric heme and an Epacadostat analogCRYSTAL STRUCTURE OF HUMAN INDOLEAMINE 2,3-DIOXYGENASE 1 (IDO1) in complex with ferric heme and an Epacadostat analog
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 PubMedHuman indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-dependent enzyme with important roles in many cellular processes and is a potential target for drug discovery against cancer and other diseases. Crystal structures of IDO1 in complex with various inhibitors have been reported. Many of these crystals belong to the same crystal form and most of the reported structures have resolutions in the range 3.2-2.3 A. Here, three new crystal forms of human IDO1 obtained by introducing a surface mutation, K116A/K117A, distant from the active site are reported. One of these crystal forms diffracted to 1.5 A resolution and can be readily used for soaking experiments to determine high-resolution structures of IDO1 in complex with the substrate tryptophan or inhibitors that coordinate the heme. In addition, this mutant was used to produce crystals of a complex with an inhibitor that targets the apo form of the enzyme under the same conditions; the structure of this complex was determined at 1.7 A resolution. Overall, this mutant represents a robust platform for determining the structures of inhibitor and substrate complexes of IDO1 at high resolution. High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form.,Luo S, Xu K, Xiang S, Chen J, Chen C, Guo C, Tong Y, Tong L Acta Crystallogr F Struct Biol Commun. 2018 Nov 1;74(Pt 11):717-724. doi:, 10.1107/S2053230X18012955. Epub 2018 Oct 17. PMID:30387777[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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