8qv7: Difference between revisions
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==Crystal structure of human TDO with alpha-methyl-L-tryptophan== | ==Crystal structure of human TDO with alpha-methyl-L-tryptophan== | ||
<StructureSection load='8qv7' size='340' side='right'caption='[[8qv7]], [[Resolution|resolution]] 2. | <StructureSection load='8qv7' size='340' side='right'caption='[[8qv7]], [[Resolution|resolution]] 2.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8qv7]] 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=8QV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QV7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8qv7]] 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=8QV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QV7 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. | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.928Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZIQ:alpha-methyl-L-tryptophan'>ZIQ</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZIQ:alpha-methyl-L-tryptophan'>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=8qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qv7 OCA], [https://pdbe.org/8qv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qv7 RCSB], [https://www.ebi.ac.uk/pdbsum/8qv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qv7 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=8qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qv7 OCA], [https://pdbe.org/8qv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qv7 RCSB], [https://www.ebi.ac.uk/pdbsum/8qv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qv7 ProSAT]</span></td></tr> | ||
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== 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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 8qv7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 06:26, 4 December 2024
Crystal structure of human TDO with alpha-methyl-L-tryptophan
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