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{{Large structure}}
 
==1H, 13C and 15N chemical shift assignments and solution structure for PARP-1 F1F2 domains in complex with a DNA single-strand break==
==1H, 13C and 15N chemical shift assignments and solution structure for PARP-1 F1F2 domains in complex with a DNA single-strand break==
<StructureSection load='2n8a' size='340' side='right' caption='[[2n8a]], [[NMR_Ensembles_of_Models | 78 NMR models]]' scene=''>
<StructureSection load='2n8a' size='340' side='right'caption='[[2n8a]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2n8a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N8A FirstGlance]. <br>
<table><tr><td colspan='2'>[[2n8a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N8A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<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 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=2n8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8a OCA], [https://pdbe.org/2n8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n8a RCSB], [https://www.ebi.ac.uk/pdbsum/2n8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8a ProSAT]</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=2n8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8a OCA], [http://pdbe.org/2n8a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n8a RCSB], [http://www.ebi.ac.uk/pdbsum/2n8a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8a ProSAT]</span></td></tr>
</table>
</table>
{{Large structure}}
== Function ==
== Function ==
[[http://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> 
[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. A burst of poly(ADP-ribose) synthesis initiates DNA damage response, whereas PARP-1 inhibition kills BRCA-deficient tumor cells selectively, providing the first anti-cancer therapy based on synthetic lethality. However, the mechanism underlying PARP-1's function remained obscure; inherent dynamics of SSBs and PARP-1's multi-domain architecture hindered structural studies. Here we reveal the structural basis of SSB detection and how multi-domain folding underlies the allosteric switch that determines PARP-1's signaling response. Two flexibly linked N-terminal zinc fingers recognize the extreme deformability of SSBs and drive co-operative, stepwise self-assembly of remaining PARP-1 domains to control the activity of the C-terminal catalytic domain. Automodifcation in cis explains the subsequent release of monomeric PARP-1 from DNA, allowing repair and replication to proceed. Our results provide a molecular framework for understanding PARP inhibitor action and, more generally, allosteric control of dynamic, multi-domain proteins.
 
Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1.,Eustermann S, Wu WF, Langelier MF, Yang JC, Easton LE, Riccio AA, Pascal JM, Neuhaus D Mol Cell. 2015 Dec 3;60(5):742-54. doi: 10.1016/j.molcel.2015.10.032. Epub 2015, Nov 25. PMID:26626479<ref>PMID:26626479</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2n8a" 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 ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Eustermann, S]]
[[Category: Large Structures]]
[[Category: Neuhaus, D]]
[[Category: Eustermann S]]
[[Category: Wu, W]]
[[Category: Neuhaus D]]
[[Category: Yang, J]]
[[Category: Wu W]]
[[Category: Transferase]]
[[Category: Yang J]]
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