View source for 5nsp


==Crystal structure of TNKS2 in complex with OD334==
<StructureSection load='5nsp' size='340' side='right'caption='[[5nsp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nsp]] 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=5NSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NSP 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=97E:1-[4-[4-(2-chlorophenyl)-5-pyrimidin-4-yl-1,2,4-triazol-3-yl]phenyl]-2-oxidanylidene-3~{H}-benzimidazole-5-carbonitrile'>97E</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5nsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nsp OCA], [https://pdbe.org/5nsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nsp RCSB], [https://www.ebi.ac.uk/pdbsum/5nsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nsp ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A structure-guided hybridization approach using two privileged substructures gave instant access to a new series of tankyrase inhibitors. The identified inhibitor 16 displays high target affinity on tankyrase 1 and 2 with a biochemical and cellular IC50 values of 29 nM, 6.3 nM and 19 nM, respectively, and high selectivity towards other Poly(ADP-ribose) polymerase enzymes. The identified inhibitor shows a favorable in-vitro ADME profile as well as good oral bioavailability in mice, rats and dogs. Critical for the approach was the utilization of an appropriate linker between 1,2,4-triazole and benzimidazolone moieties, whereby a cyclobutyl linker displayed superior affinity compared to a cyclohexane and phenyl linker.

Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach.,Anumala UR, Waaler J, Nkizinkiko Y, Ignatev A, Lazarow K, Lindemann P, Olsen PA, Murthy S, Obaji E, Majouga AG, Leonov SV, von Kries JP, Lehtio L, Krauss S, Nazare M J Med Chem. 2017 Nov 20. doi: 10.1021/acs.jmedchem.7b00883. PMID:29155568<ref>PMID:29155568</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nsp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Haikarainen T]]
[[Category: Lehtio L]]
[[Category: Nkizinkiko Y]]