4bfp

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{{STRUCTURE_4bfp| PDB=4bfp | SCENE= }}
 
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===Crystal structure of human tankyrase 2 in complex with WIKI4===
 
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{{ABSTRACT_PUBMED_23762361}}
 
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==Function==
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==Crystal structure of human tankyrase 2 in complex with WIKI4==
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[[http://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>
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<StructureSection load='4bfp' size='340' side='right'caption='[[4bfp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4bfp]] is a 2 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=4BFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BFP 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]] 2.4&#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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SWY:2-[3-[[4-(4-METHOXYPHENYL)-5-PYRIDIN-4-YL-1,2,4-TRIAZOL-3-YL]SULFANYL]PROPYL]BENZO[DE]ISOQUINOLINE-1,3-DIONE'>SWY</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=4bfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bfp OCA], [https://pdbe.org/4bfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bfp RCSB], [https://www.ebi.ac.uk/pdbsum/4bfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bfp ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Recently a novel inhibitor of Wnt signaling was discovered. The compound, WIKI4, was found to act through tankyrase inhibition and regulate beta-catenin levels in many cancer cell lines and human embryonic stem cells. Here we confirm that WIKI4 is a high potency tankyrase inhibitor and that it selectively inhibits tankyrases over other ARTD enzymes tested. The binding mode of the compound to tankyrase 2 was determined by protein X-ray crystallography to 2.4 A resolution. The structure revealed a novel binding mode to the adenosine subsite of the donor NAD(+) binding groove of the catalytic domain. Our results form a structural basis for further development of potent and selective tankyrase inhibitors based on the WIKI4 scaffold.
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==About this Structure==
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Structural Basis and Selectivity of Tankyrase Inhibition by a Wnt Signaling Inhibitor WIKI4.,Haikarainen T, Venkannagari H, Narwal M, Obaji E, Lee HW, Nkizinkiko Y, Lehtio L PLoS One. 2013 Jun 6;8(6):e65404. doi: 10.1371/journal.pone.0065404. Print 2013. PMID:23762361<ref>PMID:23762361</ref>
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[[4bfp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BFP OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:023762361</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 4bfp" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Haikarainen, T.]]
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[[Category: Large Structures]]
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[[Category: Lehtio, L.]]
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[[Category: Haikarainen T]]
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[[Category: Narwal, M.]]
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[[Category: Lehtio L]]
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[[Category: Adp-ribosylation]]
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[[Category: Narwal M]]
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[[Category: Diphtheria toxin like fold]]
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[[Category: Protein-ligand complex]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of human tankyrase 2 in complex with WIKI4

PDB ID 4bfp

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