View source for 4tk0


==Crystal Structure of human Tankyrase 2 in complex with DPQ.==
<StructureSection load='4tk0' size='340' side='right'caption='[[4tk0]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4tk0]] 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=4TK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TK0 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32Z:5-[4-(PIPERIDIN-1-YL)BUTOXY]-3,4-DIHYDROISOQUINOLIN-1(2H)-ONE'>32Z</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=4tk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tk0 OCA], [https://pdbe.org/4tk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tk0 RCSB], [https://www.ebi.ac.uk/pdbsum/4tk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tk0 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 ==
The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated beta-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, the high-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors.

Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2.,Qiu W, Lam R, Voytyuk O, Romanov V, Gordon R, Gebremeskel S, Vodsedalek J, Thompson C, Beletskaya I, Battaile KP, Pai EF, Rottapel R, Chirgadze NY Acta Crystallogr D Biol Crystallogr. 2014 Oct;70(Pt 10):2740-53. doi:, 10.1107/S1399004714017660. Epub 2014 Sep 27. PMID:25286857<ref>PMID:25286857</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4tk0" 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: Battaile KP]]
[[Category: Beletskaya I]]
[[Category: Chirgadze NY]]
[[Category: Gebremeskel S]]
[[Category: Gordon R]]
[[Category: Lam R]]
[[Category: Pai EF]]
[[Category: Qiu W]]
[[Category: Romanov V]]
[[Category: Thompson C]]
[[Category: Vodsedalek J]]