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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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SE2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3goy|3goy]], [[3smi|3smi]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAL2, KIAA1268, PARP14 ([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=3se2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3se2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3se2 RCSB], [http://www.ebi.ac.uk/pdbsum/3se2 PDBsum]</span></td></tr> | |||
</table> | |||
<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> | |||
==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: Arrowsmith, C H | [[Category: Arrowsmith, C H]] | ||
[[Category: Berglund, H | [[Category: Berglund, H]] | ||
[[Category: Bountra, C | [[Category: Bountra, C]] | ||
[[Category: Collins, R | [[Category: Collins, R]] | ||
[[Category: Edwards, A M | [[Category: Edwards, A M]] | ||
[[Category: Ekblad, T | [[Category: Ekblad, T]] | ||
[[Category: Graslund, S | [[Category: Graslund, S]] | ||
[[Category: Karlberg, T | [[Category: Karlberg, T]] | ||
[[Category: Kouznetsova, E | [[Category: Kouznetsova, E]] | ||
[[Category: Moche, M | [[Category: Moche, M]] | ||
[[Category: Nordlund, P | [[Category: Nordlund, P]] | ||
[[Category: Nyman, T | [[Category: Nyman, T]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Schuler , H | [[Category: Schuler , H]] | ||
[[Category: Schutz, P | [[Category: Schutz, P]] | ||
[[Category: Siponen, M I | [[Category: Siponen, M I]] | ||
[[Category: Thorsell, A G | [[Category: Thorsell, A G]] | ||
[[Category: Tresaugues, L | [[Category: Tresaugues, L]] | ||
[[Category: Weigelt, J | [[Category: Weigelt, J]] | ||
[[Category: Adp-ribosylation]] | [[Category: Adp-ribosylation]] | ||
[[Category: Diphtheria toxin like fold]] | [[Category: Diphtheria toxin like fold]] | ||
[[Category: Nad+]] | [[Category: Nad+]] | ||
[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 14:33, 9 December 2014
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
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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