View source for 6cxv


==Structure of the S167H mutant of human indoleamine 2,3 dioxygenase in complex with tryptophan and cyanide==
<StructureSection load='6cxv' size='340' side='right'caption='[[6cxv]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cxv]] 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=6CXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CXV 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYN:CYANIDE+ION'>CYN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene>, <scene name='pdbligand=ZCW:2-(1H-indol-3-yl)ethanol'>ZCW</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=6cxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cxv OCA], [https://pdbe.org/6cxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cxv RCSB], [https://www.ebi.ac.uk/pdbsum/6cxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cxv 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 ==
Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan dioxygenase (hTDO) catalyze the same dioxygenation reaction of Trp to generate N-formyl kynurenine (NFK). They share high structural similarity, especially in the active site. However, hIDO1 possesses a unique inhibitory substrate binding site (Si) that is absent in hTDO. In addition, in hIDO1, the indoleamine group of the substrate Trp is H-bonded to S167 through a bridging water, while that in hTDO is directly H-bonded to H76. Here we show that Trp binding to the Si site or the mutation of S167 to histidine in hIDO1 retards its turnover activity, and that the inhibited activity can be rescued by an effector, 3-indole ethanol (IDE). Kinetic studies reveal that the inhibited activity introduced by Trp binding to the Si site is a result of retarded recombination of the ferryl moiety with Trp epoxide to form NFK, and that IDE reverses the effect by preventing Trp from binding to the Si site. In contrast, the abolished activity induced by the S167H mutation is primarily a result of ~5000-fold reduction in the O2 binding rate constant, possibly due to the blockage of a ligand delivery tunnel, and that IDE binding to the Si site reverses the effect by reopening the tunnel. The data offer new insights into structure-based design of hIDO1-selective inhibitors.

Inhibition Mechanisms of Human Indoleamine 2,3 Dioxygenase 1.,Lewis-Ballester A, Karkashon S, Batabyal D, Poulos TL, Yeh SR J Am Chem Soc. 2018 Jun 13. doi: 10.1021/jacs.8b03691. PMID:29897749<ref>PMID:29897749</ref>

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

==See Also==
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Batabyal D]]
[[Category: Karkashon S]]
[[Category: Lewis-Ballester A]]
[[Category: Poulos TL]]
[[Category: Yeh S-R]]