3l3l

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==PARP complexed with A906894==
==PARP complexed with A906894==
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<StructureSection load='3l3l' size='340' side='right' caption='[[3l3l]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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<StructureSection load='3l3l' size='340' side='right'caption='[[3l3l]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3l3l]] is a 1 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=3L3L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L3L FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3l3l]] 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=3L3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L3L 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=L3L:3-OXO-2-PIPERIDIN-4-YL-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>L3L</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2rcw|2rcw]], [[2rd6|2rd6]], [[3gjw|3gjw]], [[3gn7|3gn7]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L3L:3-OXO-2-PIPERIDIN-4-YL-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>L3L</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP1, ADPRT, PPOL ([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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l3l OCA], [https://pdbe.org/3l3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l3l RCSB], [https://www.ebi.ac.uk/pdbsum/3l3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l3l ProSAT]</span></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=3l3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l3l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l3l RCSB], [http://www.ebi.ac.uk/pdbsum/3l3l PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
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Through conformational restriction of a benzamide by formation of a seven-membered hydrogen-bond with an oxindole carbonyl group, a series of PARP inhibitors was designed for appropriate orientation for binding to the PARP surface. This series of compounds with a 3-oxoisoindoline-4-carboxamide core structure, displayed modest to good activity against PARP-1 in both intrinsic and cellular assays. SAR studies at the lactam nitrogen of the pharmacophore have suggested that a secondary or tertiary amine is important for cellular potency. An X-ray structure of compound 1e bound to the protein confirmed the formation of a seven-membered intramolecular hydrogen bond. Though revealed previously in peptides, this type of seven-membered intramolecular hydrogen bond is rarely observed in small molecules. Largely due to the formation of the intramolecular hydrogen bond, the 3-oxoisoindoline-4-carboxamide core structure appears to be planar in the X-ray structure. An additional hydrogen bond interaction of the piperidine nitrogen to Gly-888 also contributes to the binding affinity of 1e to PARP-1.
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Discovery and SAR of substituted 3-oxoisoindoline-4-carboxamides as potent inhibitors of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer.,Gandhi VB, Luo Y, Liu X, Shi Y, Klinghofer V, Johnson EF, Park C, Giranda VL, Penning TD, Zhu GD Bioorg Med Chem Lett. 2010 Feb 1;20(3):1023-6. Epub 2009 Dec 14. PMID:20045315<ref>PMID:20045315</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]]
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*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Park, C H]]
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[[Category: Large Structures]]
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[[Category: Adp-ribosylation]]
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[[Category: Park CH]]
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[[Category: Dna damage]]
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[[Category: Dna repair]]
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[[Category: Dna-binding]]
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[[Category: Glycosyltransferase]]
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[[Category: Metal-binding]]
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[[Category: Nad]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Protein-inhibitor complex]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

PARP complexed with A906894

PDB ID 3l3l

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