6tuz: Difference between revisions
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<StructureSection load='6tuz' size='340' side='right'caption='[[6tuz]], [[Resolution|resolution]] 1.24Å' scene=''> | <StructureSection load='6tuz' size='340' side='right'caption='[[6tuz]], [[Resolution|resolution]] 1.24Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TUZ 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]] 1.24Å</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]] 1.24Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TEP:THEOPHYLLINE'>TEP</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TEP:THEOPHYLLINE'>TEP</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=6tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tuz OCA], [https://pdbe.org/6tuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tuz RCSB], [https://www.ebi.ac.uk/pdbsum/6tuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tuz 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=6tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tuz OCA], [https://pdbe.org/6tuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tuz RCSB], [https://www.ebi.ac.uk/pdbsum/6tuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tuz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Jones EY]] | [[Category: Jones EY]] | ||
[[Category: Zhao Y]] | [[Category: Zhao Y]] | ||
Latest revision as of 12:13, 9 October 2024
Theophylline-Notum complexTheophylline-Notum complex
Structural highlights
Publication Abstract from PubMedNotum inhibits Wnt signalling via enzymatic delipidation of Wnt ligands. Restoration of Wnt signalling by small molecule inhibition of Notum may be of therapeutic benefit in a number of pathologies including Alzheimer's disease. Here we report Notum activity can be inhibited by caffeine (IC50 19 microM), but not by demethylated caffeine metabolites: paraxanthine, theobromine and theophylline. Cellular luciferase assays show Notum-suppressed Wnt3a function can be restored by caffeine with an EC50 of 46 microM. The dissociation constant (Kd) between Notum and caffeine is 85 microM as measured by surface plasmon resonance. High-resolution crystal structures of Notum complexes with caffeine and its minor metabolite theophylline show both compounds bind at the centre of the enzymatic pocket, overlapping the position of the natural substrate palmitoleic lipid, but using different binding modes. The structural information reported here may be of relevance for the design of more potent brain-accessible Notum inhibitors. Caffeine inhibits Notum activity by binding at the catalytic pocket.,Zhao Y, Ren J, Hillier J, Lu W, Jones EY Commun Biol. 2020 Oct 8;3(1):555. doi: 10.1038/s42003-020-01286-5. PMID:33033363[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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