4krs

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{{STRUCTURE_4krs| PDB=4krs | SCENE= }}
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==Tankyrase-1 complexed with small molecule inhibitor==
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===Tankyrase-1 complexed with small molecule inhibitor===
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<StructureSection load='4krs' size='340' side='right' caption='[[4krs]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23879431}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4krs]] 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=4KRS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KRS FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1SX:4-TERT-BUTYL-N-(5,6-DIHYDRO[1,3]THIAZOLO[2,3-C][1,2,4]TRIAZOL-3-YL)BENZAMIDE'>1SX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4krs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4krs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4krs RCSB], [http://www.ebi.ac.uk/pdbsum/4krs PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well-known, herein we report the discovery and evaluation of a novel nicotinamide isostere that demonstrates selectivity over other PARP family members. We demonstrate the utilization of lipophilic efficiency-based structure-efficiency relationships (SER) to rapidly drive the evaluation of this series. These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization.
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==Function==
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Structure-Efficiency Relationship of [1,2,4]Triazol-3-ylamines as Novel Nicotinamide Isosteres that Inhibit Tankyrases.,Shultz MD, Majumdar D, Chin DN, Fortin PD, Feng Y, Gould T, Kirby CA, Stams T, Waters NJ, Shao W J Med Chem. 2013 Aug 14. PMID:23879431<ref>PMID:23879431</ref>
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[[http://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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4krs]] 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=4KRS OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023879431</ref><references group="xtra"/><references/>
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*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]]
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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: Kirby, C.]]
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[[Category: Kirby, C]]
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[[Category: Stams, T.]]
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[[Category: Stams, T]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 14:59, 21 December 2014

Tankyrase-1 complexed with small molecule inhibitor

4krs, resolution 2.29Å

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