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==Crystal structure of a photochemical intermediate of human indoleamine 2,3-dioxygenase 1 in complex with carbon monoxide and tryptophan== | ==Crystal structure of a photochemical intermediate of human indoleamine 2,3-dioxygenase 1 in complex with carbon monoxide and tryptophan== | ||
<StructureSection load='6ubp' size='340' side='right'caption='[[6ubp]]' scene=''> | <StructureSection load='6ubp' size='340' side='right'caption='[[6ubp]], [[Resolution|resolution]] 2.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UBP FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UBP FirstGlance]. <br> | ||
</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=6ubp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ubp OCA], [https://pdbe.org/6ubp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ubp RCSB], [https://www.ebi.ac.uk/pdbsum/6ubp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ubp ProSAT]</span></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]] 2.95Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</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=6ubp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ubp OCA], [https://pdbe.org/6ubp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ubp RCSB], [https://www.ebi.ac.uk/pdbsum/6ubp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ubp ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human indoleamine 2,3-dioxygenase 1 (hIDO1) and human tryptophan dioxygenase (hTDO) are two important heme proteins that degrade the essential amino acid, l-tryptophan (Trp), along the kynurenine pathway. The two enzymes share a similar active site structure and an analogous catalytic mechanism, but they exhibit a variety of distinct functional properties. Here we used carbon monoxide (CO) as a structural probe to interrogate how the functionalities of the two enzymes are encoded in their structures. With X-ray crystallography, we detected an unexpected photochemical intermediate trapped in a crystal of the hIDO1-CO-Trp complex, where CO is photolyzed from the heme iron by X-rays at cryogenic temperatures (100 K). The CO photolysis triggers a large-scale migration of the substrate Trp, as well as the photolyzed CO, from the active site to a temporary binding site, Sa*. It is accompanied by a large conformational change to an active site loop, JK-Loop(C), despite the severely restricted protein motion under the frozen conditions, which highlights the remarkable conformational plasticity of the hIDO1 protein. Comparative studies of a crystal of the hTDO-CO-Trp complex show that CO and Trp remain bound in the active site under comparable X-ray illumination, indicating a much more rigid protein architecture. The data offer important new insights into the structure and function relationships of the heme-based dioxygenases and provide new guidelines for structure-based design of inhibitors targeting them. | |||
Conformational Plasticity in Human Heme-Based Dioxygenases.,Pham KN, Lewis-Ballester A, Yeh SR J Am Chem Soc. 2020 Dec 29. doi: 10.1021/jacs.0c09970. PMID:33373218<ref>PMID:33373218</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ubp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 16:10, 6 November 2024
Crystal structure of a photochemical intermediate of human indoleamine 2,3-dioxygenase 1 in complex with carbon monoxide and tryptophanCrystal structure of a photochemical intermediate of human indoleamine 2,3-dioxygenase 1 in complex with carbon monoxide and tryptophan
Structural highlights
Publication Abstract from PubMedHuman indoleamine 2,3-dioxygenase 1 (hIDO1) and human tryptophan dioxygenase (hTDO) are two important heme proteins that degrade the essential amino acid, l-tryptophan (Trp), along the kynurenine pathway. The two enzymes share a similar active site structure and an analogous catalytic mechanism, but they exhibit a variety of distinct functional properties. Here we used carbon monoxide (CO) as a structural probe to interrogate how the functionalities of the two enzymes are encoded in their structures. With X-ray crystallography, we detected an unexpected photochemical intermediate trapped in a crystal of the hIDO1-CO-Trp complex, where CO is photolyzed from the heme iron by X-rays at cryogenic temperatures (100 K). The CO photolysis triggers a large-scale migration of the substrate Trp, as well as the photolyzed CO, from the active site to a temporary binding site, Sa*. It is accompanied by a large conformational change to an active site loop, JK-Loop(C), despite the severely restricted protein motion under the frozen conditions, which highlights the remarkable conformational plasticity of the hIDO1 protein. Comparative studies of a crystal of the hTDO-CO-Trp complex show that CO and Trp remain bound in the active site under comparable X-ray illumination, indicating a much more rigid protein architecture. The data offer important new insights into the structure and function relationships of the heme-based dioxygenases and provide new guidelines for structure-based design of inhibitors targeting them. Conformational Plasticity in Human Heme-Based Dioxygenases.,Pham KN, Lewis-Ballester A, Yeh SR J Am Chem Soc. 2020 Dec 29. doi: 10.1021/jacs.0c09970. PMID:33373218[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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