3u9h: Difference between revisions
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[[ | ==Complex structure of human tankyrase 2 with nicotinamide== | ||
<StructureSection load='3u9h' size='340' side='right' caption='[[3u9h]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3u9h]] 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=3U9H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U9H FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNKS2, PARP5B, TANK2, TNKL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<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> | |||
<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=3u9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u9h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u9h RCSB], [http://www.ebi.ac.uk/pdbsum/3u9h PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tankyrases are poly(ADP-ribose) polymerases that have many cellular functions. They play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions. These features make tankyrases potential targets for treatment of cancer. We report here crystal structures of human tankyrase 2 catalytic fragment in complex with a by-product, nicotinamide and with selective inhibitors of tankyrases (IWR-1) and PARPs 1 and 2 (olaparib). Binding of these inhibitors to tankyrase 2 induce specific conformational changes. The crystal structures explain the selectivity of the inhibitors, reveal the flexibility of a substrate binding loop and explain existing structure-activity relationship data. The first crystal structure of a PARP enzyme in complex with a potent inhibitor, IWR-1, which does not bind to the widely-utilized nicotinamide-binding site makes the structure valuable also for development of PARP inhibitors in general. | |||
Structural Basis of Selective Inhibition of Human Tankyrases.,Narwal M, Venkannagari H, Lehtio L J Med Chem. 2012 Jan 10. PMID:22233320<ref>PMID:22233320</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]] | *[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Lehtio, L | [[Category: Lehtio, L]] | ||
[[Category: Narwal, M | [[Category: Narwal, M]] | ||
[[Category: Adp-ribosylation]] | [[Category: Adp-ribosylation]] | ||
[[Category: Diphtheria toxin like fold]] | [[Category: Diphtheria toxin like fold]] | ||
[[Category: Protein-ligand complex]] | [[Category: Protein-ligand complex]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
