2rf5: Difference between revisions
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==Crystal structure of human tankyrase 1- catalytic PARP domain== | |||
<StructureSection load='2rf5' size='340' side='right'caption='[[2rf5]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2rf5]] 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=2RF5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RF5 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2rf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rf5 OCA], [https://pdbe.org/2rf5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rf5 RCSB], [https://www.ebi.ac.uk/pdbsum/2rf5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rf5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rf/2rf5_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2rf5 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tankyrases are recently discovered proteins implicated in many important functions in the cell including telomere homeostasis and mitosis. Tankyrase modulates the activity of target proteins through poly(ADP-ribosyl)ation, and here we report the structure of the catalytic poly(ADP-ribose) polymerase (PARP) domain of human tankyrase 1. This is the first structure of a PARP domain from the tankyrase subfamily. The present structure reveals that tankyrases contain a short zinc-binding motif, which has not been predicted. Tankyrase activity contributes to telomere elongation observed in various cancer cells and tankyrase inhibition has been suggested as a potential route for cancer therapy. In comparison with other PARPs, significant structural differences are observed in the regions lining the substrate-binding site of tankyrase 1. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and tankyrase inhibitors, in particular. | |||
Zinc binding catalytic domain of human tankyrase 1.,Lehtio L, Collins R, van den Berg S, Johansson A, Dahlgren LG, Hammarstrom M, Helleday T, Holmberg-Schiavone L, Karlberg T, Weigelt J J Mol Biol. 2008 May 23;379(1):136-45. Epub 2008 Apr 3. PMID:18436240<ref>PMID:18436240</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2rf5" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]] | *[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Arrowsmith CH]] | ||
[[Category: Berglund | [[Category: Berglund H]] | ||
[[Category: Busam | [[Category: Busam R]] | ||
[[Category: Collins | [[Category: Collins R]] | ||
[[Category: Dahlgren | [[Category: Dahlgren LG]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Flodin | [[Category: Flodin S]] | ||
[[Category: Flores | [[Category: Flores A]] | ||
[[Category: Graslund | [[Category: Graslund S]] | ||
[[Category: Hammarstrom | [[Category: Hammarstrom M]] | ||
[[Category: Herman | [[Category: Herman MD]] | ||
[[Category: Holmberg-Schiavone | [[Category: Holmberg-Schiavone L]] | ||
[[Category: Johansson | [[Category: Johansson I]] | ||
[[Category: Kallas | [[Category: Kallas A]] | ||
[[Category: Karlberg | [[Category: Karlberg T]] | ||
[[Category: Kotenyova | [[Category: Kotenyova T]] | ||
[[Category: Lehtio | [[Category: Lehtio L]] | ||
[[Category: Moche | [[Category: Moche M]] | ||
[[Category: Nordlund | [[Category: Nordlund P]] | ||
[[Category: Nyman | [[Category: Nyman T]] | ||
[[Category: Persson | [[Category: Persson C]] | ||
[[Category: Sagemark J]] | |||
[[Category: Sagemark | [[Category: Sundstrom M]] | ||
[[Category: Sundstrom | [[Category: Thorsell AG]] | ||
[[Category: Thorsell | [[Category: Tresaugues L]] | ||
[[Category: Tresaugues | [[Category: Weigelt J]] | ||
[[Category: Weigelt | [[Category: Welin M]] | ||
[[Category: Welin | [[Category: Van den Berg S]] | ||
[[Category: | |||