8r5q
From Proteopedia
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<table><tr><td colspan='2'>[[8r5q]] is a 4 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=8R5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R5Q FirstGlance]. <br> | <table><tr><td colspan='2'>[[8r5q]] is a 4 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=8R5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R5Q 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]] 2.62Å</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]] 2.62Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y5N:3-chloranyl-~{N}-[(1~{S})-1-(6-chloranylpyridin-3-yl)-2-phenyl-ethyl]aniline'>Y5N</scene>, <scene name='pdbligand=ZIQ: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y5N:3-chloranyl-~{N}-[(1~{S})-1-(6-chloranylpyridin-3-yl)-2-phenyl-ethyl]aniline'>Y5N</scene>, <scene name='pdbligand=ZIQ:(2~{S})-2-azanyl-3-(1~{H}-indol-3-yl)-2-methyl-propanoic+acid'>ZIQ</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=8r5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r5q OCA], [https://pdbe.org/8r5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r5q RCSB], [https://www.ebi.ac.uk/pdbsum/8r5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r5q 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=8r5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r5q OCA], [https://pdbe.org/8r5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r5q RCSB], [https://www.ebi.ac.uk/pdbsum/8r5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r5q ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/T23O_HUMAN T23O_HUMAN] Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity). | [https://www.uniprot.org/uniprot/T23O_HUMAN T23O_HUMAN] Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tryptophan-2,3-dioxygenase (TDO2) and indoleamine-2,3-dioxygenase (IDO1) are structurally distinct heme enzymes that catalyze the conversion of L-tryptophan to N-formyl-kynurenine, and play important roles in metabolism, inflammation, and tumor immune surveillance. The enzymes can adopt an inactive, heme-free (apo) state or an active, heme-containing (holo) state, with the balance between them varying dynamically according to biological conditions. Inhibitors of holo-TDO2 are known but, despite several advantages of the heme-free state as a drug target, no inhibitors of apo-TDO2 have been reported. We describe the discovery of the first apo-TDO2 binding inhibitors, to our knowledge, and their inhibition of cellular TDO2 activity at low nanomolar concentrations. The crystal structure of a potent, small molecule inhibitor bound to apo-TDO2 reveals its detailed binding interactions within the large, hydrophobic heme binding pocket of the active site. | ||
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| + | Discovery and binding mode of small molecule inhibitors of the apo form of human TDO2.,Lotz-Jenne C, Lange R, Cren S, Bourquin G, Goglia L, Kimmerlin T, Wicki M, Muller M, Artico N, Ackerknecht S, Pfaff P, Joesch C, Mac Sweeney A Sci Rep. 2024 Nov 14;14(1):27937. doi: 10.1038/s41598-024-78981-4. PMID:39537789<ref>PMID:39537789</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8r5q" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of apo TDO with a bound inhibitor
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