9oo6

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m (Protected "9oo6" [edit=sysop:move=sysop])
Current revision (08:17, 11 December 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9oo6 is ON HOLD until Paper Publication
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==Human PORCN bound to inhibitor C59==
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<StructureSection load='9oo6' size='340' side='right'caption='[[9oo6]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9oo6]] is a 1 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=9OO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OO6 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">Electron Microscopy, [[Resolution|Resolution]] 2.39&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CC5:2-[4-(2-methylpyridin-4-yl)phenyl]-~{N}-(4-pyridin-3-ylphenyl)ethanamide'>A1CC5</scene>, <scene name='pdbligand=AV0:2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>AV0</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=9oo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9oo6 OCA], [https://pdbe.org/9oo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9oo6 RCSB], [https://www.ebi.ac.uk/pdbsum/9oo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9oo6 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PORCN_HUMAN PORCN_HUMAN] Focal dermal hypoplasia;Colobomatous microphthalmia. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/PORCN_HUMAN PORCN_HUMAN] Protein-serine O-palmitoleoyltransferase that acts as a key regulator of the Wnt signaling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors.[UniProtKB:Q9JJJ7]<ref>PMID:12034504</ref> <ref>PMID:20826466</ref> <ref>PMID:24292069</ref> [https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Wnt signalling is essential for embryonic development and tissue homeostasis, and its dysregulation is associated with multiple types of cancer. Porcupine (PORCN), an endoplasmic reticulum (ER)-resident membrane-bound O-acyltransferase, catalyses the palmitoleoylation of all 19 human Wnts-a critical modification required for their secretion and activity. This central role makes PORCN an attractive therapeutic target for Wnt-driven cancers, with several inhibitors currently in clinical trials. Here, we present high-resolution cryo-electron microscopy structures of human PORCN in complex with the inhibitors C59 (2.4 A) and ETC159 (2.6 A), as well as in a ligand-free state (3.3 A). These structures reveal critical ordered water molecules that form a hydrogen-bonding network within the active site, mediating inhibitor binding. Our docking simulations of diverse PORCN inhibitors demonstrate that despite their different chemical scaffolds, these compounds adopt similar conformations within the acyl-CoA binding site and are also engaged through a conserved water molecule. Our findings provide a structural foundation for the rational design of next-generation PORCN inhibitors with improved pharmacological properties for cancer therapy.
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Authors: Black, K.A., Venugopal, H., Glukhova, A.
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Structural basis for Porcupine inhibition.,Black KA, Mobbs JI, Venugopal H, Dite TA, Leis A, Wong LL, Dagley LF, Thal DM, Glukhova A Commun Chem. 2025 Nov 12;8(1):348. doi: 10.1038/s42004-025-01726-5. PMID:41225132<ref>PMID:41225132</ref>
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Description: Human PORCN bound to inhibitor C59
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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: Venugopal, H]]
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<div class="pdbe-citations 9oo6" style="background-color:#fffaf0;"></div>
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[[Category: Black, K.A]]
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== References ==
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[[Category: Glukhova, A]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Black KA]]
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[[Category: Glukhova A]]
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[[Category: Venugopal H]]

Current revision

Human PORCN bound to inhibitor C59

PDB ID 9oo6

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