6tfm

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'''Unreleased structure'''
 
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The entry 6tfm is ON HOLD
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==Frizzled8 CRD==
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<StructureSection load='6tfm' size='340' side='right'caption='[[6tfm]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6tfm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TFM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TFM FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.343&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tfm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tfm OCA], [https://pdbe.org/6tfm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tfm RCSB], [https://www.ebi.ac.uk/pdbsum/6tfm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tfm ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FZD8_MOUSE FZD8_MOUSE] Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes (By similarity). The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.<ref>PMID:10395542</ref> <ref>PMID:10097073</ref> <ref>PMID:15454084</ref> <ref>PMID:16543246</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Misregulation of Wnt signaling is common in human cancer. The development of small molecule inhibitors against the Wnt receptor, frizzled (FZD), may have potential in cancer therapy. During small molecule screens, we observed binding of carbamazepine to the cysteine-rich domain (CRD) of the Wnt receptor FZD8 using surface plasmon resonance (SPR). Cellular functional assays demonstrated that carbamazepine can suppress FZD8-mediated Wnt/beta-catenin signaling. We determined the crystal structure of the complex at 1.7 A resolution, which reveals that carbamazepine binds at a novel pocket on the FZD8 CRD. The unique residue Tyr52 discriminates FZD8 from the closely related FZD5 and other FZDs for carbamazepine binding. The first small molecule-bound FZD structure provides a basis for anti-FZD drug development. Furthermore, the observed carbamazepine-mediated Wnt signaling inhibition may help to explain the phenomenon of bone loss and increased adipogenesis in some patients during long-term carbamazepine treatment.
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Authors: Zhao, Y., Jones, E.Y.
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Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8.,Zhao Y, Ren J, Hillier J, Lu W, Jones EY J Med Chem. 2020 Feb 25. doi: 10.1021/acs.jmedchem.9b02020. PMID:32049522<ref>PMID:32049522</ref>
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Description: Frizzled8 CRD
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Zhao, Y]]
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<div class="pdbe-citations 6tfm" style="background-color:#fffaf0;"></div>
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[[Category: Jones, E.Y]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Jones EY]]
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[[Category: Zhao Y]]

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Frizzled8 CRD

PDB ID 6tfm

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