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==Human poly(ADP-ribose) polymerase 14 (PARP14/ARTD8) - catalytic domain in complex with 6(5H)-phenanthridinone== | |||
<StructureSection load='3se2' size='340' side='right'caption='[[3se2]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3se2]] 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=3SE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SE2 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=3AB:3-AMINOBENZAMIDE'>3AB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LDR:PHENANTHRIDIN-6(5H)-ONE'>LDR</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=3se2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3se2 OCA], [https://pdbe.org/3se2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3se2 RCSB], [https://www.ebi.ac.uk/pdbsum/3se2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3se2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PAR14_HUMAN PAR14_HUMAN] Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibitors of poly-ADP-ribose polymerase (PARP) family proteins are currently in clinical trials as cancer therapeutics, yet the specificity of many of these compounds is unknown. Here we evaluated a series of 185 small-molecule inhibitors, including research reagents and compounds being tested clinically, for the ability to bind to the catalytic domains of 13 of the 17 human PARP family members including the tankyrases, TNKS1 and TNKS2. Many of the best-known inhibitors, including TIQ-A, 6(5H)-phenanthridinone, olaparib, ABT-888 and rucaparib, bound to several PARP family members, suggesting that these molecules lack specificity and have promiscuous inhibitory activity. We also determined X-ray crystal structures for five TNKS2 ligand complexes and four PARP14 ligand complexes. In addition to showing that the majority of PARP inhibitors bind multiple targets, these results provide insight into the design of new inhibitors. | |||
Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors.,Wahlberg E, Karlberg T, Kouznetsova E, Markova N, Macchiarulo A, Thorsell AG, Pol E, Frostell A, Ekblad T, Oncu D, Kull B, Robertson GM, Pellicciari R, Schuler H, Weigelt J Nat Biotechnol. 2012 Feb 19. doi: 10.1038/nbt.2121. PMID:22343925<ref>PMID:22343925</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3se2" 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: Arrowsmith | [[Category: Large Structures]] | ||
[[Category: Berglund | [[Category: Arrowsmith CH]] | ||
[[Category: Bountra | [[Category: Berglund H]] | ||
[[Category: Collins | [[Category: Bountra C]] | ||
[[Category: Edwards | [[Category: Collins R]] | ||
[[Category: Ekblad | [[Category: Edwards AM]] | ||
[[Category: Graslund | [[Category: Ekblad T]] | ||
[[Category: Karlberg | [[Category: Graslund S]] | ||
[[Category: Kouznetsova | [[Category: Karlberg T]] | ||
[[Category: Moche | [[Category: Kouznetsova E]] | ||
[[Category: Nordlund | [[Category: Moche M]] | ||
[[Category: Nyman | [[Category: Nordlund P]] | ||
[[Category: Nyman T]] | |||
[[Category: Schuler | [[Category: Schuler H]] | ||
[[Category: Schutz | [[Category: Schutz P]] | ||
[[Category: Siponen | [[Category: Siponen MI]] | ||
[[Category: Thorsell | [[Category: Thorsell AG]] | ||
[[Category: Tresaugues | [[Category: Tresaugues L]] | ||
[[Category: Weigelt | [[Category: Weigelt J]] | ||
Latest revision as of 05:23, 21 November 2024
Human poly(ADP-ribose) polymerase 14 (PARP14/ARTD8) - catalytic domain in complex with 6(5H)-phenanthridinoneHuman poly(ADP-ribose) polymerase 14 (PARP14/ARTD8) - catalytic domain in complex with 6(5H)-phenanthridinone
Structural highlights
FunctionPAR14_HUMAN Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity. Publication Abstract from PubMedInhibitors of poly-ADP-ribose polymerase (PARP) family proteins are currently in clinical trials as cancer therapeutics, yet the specificity of many of these compounds is unknown. Here we evaluated a series of 185 small-molecule inhibitors, including research reagents and compounds being tested clinically, for the ability to bind to the catalytic domains of 13 of the 17 human PARP family members including the tankyrases, TNKS1 and TNKS2. Many of the best-known inhibitors, including TIQ-A, 6(5H)-phenanthridinone, olaparib, ABT-888 and rucaparib, bound to several PARP family members, suggesting that these molecules lack specificity and have promiscuous inhibitory activity. We also determined X-ray crystal structures for five TNKS2 ligand complexes and four PARP14 ligand complexes. In addition to showing that the majority of PARP inhibitors bind multiple targets, these results provide insight into the design of new inhibitors. Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors.,Wahlberg E, Karlberg T, Kouznetsova E, Markova N, Macchiarulo A, Thorsell AG, Pol E, Frostell A, Ekblad T, Oncu D, Kull B, Robertson GM, Pellicciari R, Schuler H, Weigelt J Nat Biotechnol. 2012 Feb 19. doi: 10.1038/nbt.2121. PMID:22343925[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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