2n8a - Revision history

OCA at 07:04, 1 May 2024

2024-05-01T07:04:12Z

← Older revision		Revision as of 07:04, 1 May 2024
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	== Structural highlights ==		== Structural highlights ==
	<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>		<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" id="ligandDat"><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='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='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'>[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>
	</table>		</table>
	== Function ==		== Function ==
	[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>		[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®/PubMed®, 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==

OCA at 10:23, 15 March 2023

2023-03-15T10:23:14Z

← Older revision		Revision as of 10:23, 15 March 2023
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	==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 [https://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 [https://proteopedia.org/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" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PARP1, ADPRT, PPOL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [https://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'>[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>
	</table>		</table>
	== Function ==		== Function ==
	[[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>		[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Eustermann, S]]		[[Category: Eustermann S]]
	[[Category: Neuhaus, D]]		[[Category: Neuhaus D]]
	[[Category: Wu, W]]		[[Category: Wu W]]
	[[Category: Yang, J]]		[[Category: Yang J]]
	~~[[Category: Transferase~~]]

OCA at 15:41, 8 June 2021

2021-06-08T15:41:53Z

← Older revision		Revision as of 15:41, 8 June 2021
Line 1:		Line 1:
	~~{{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]], [[NMR_Ensembles_of_Models \| 78 NMR models]]' 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/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 [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='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='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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PARP1, ADPRT, PPOL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [https://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=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>		<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>
	</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:

	==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/>
Line 29:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Eustermann, S]]		[[Category: Eustermann, S]]
	[[Category: Neuhaus, D]]		[[Category: Neuhaus, D]]

OCA at 17:09, 15 August 2018

2018-08-15T17:09:06Z

← Older revision		Revision as of 17:09, 15 August 2018
Line 3:		Line 3:
	<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]], [[NMR_Ensembles_of_Models \| 78 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2n8a]] is a 2 chain structure. 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 [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>
	</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='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='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=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>		<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>
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	</div>		</div>
	<div class="pdbe-citations 2n8a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2n8a" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Eustermann, S]]		[[Category: Eustermann, S]]
	[[Category: Neuhaus, D]]		[[Category: Neuhaus, D]]

OCA at 14:13, 5 October 2016

2016-10-05T14:13:31Z

← Older revision		Revision as of 14:13, 5 October 2016
Line 1:		Line 1:
	==~~NMR~~ solution structure ~~and assignments~~==		{{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==
	<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]], [[NMR_Ensembles_of_Models \| 78 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 5:		Line 6:
	</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='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=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]</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}}		{{Large structure}}

OCA at 06:18, 23 December 2015

2015-12-23T06:18:53Z

← Older revision		Revision as of 06:18, 23 December 2015
Line 10:		Line 10:
	== 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>		[[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>
			<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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 2n8a" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:14, 2 December 2015

2015-12-02T16:14:26Z

← Older revision		Revision as of 16:14, 2 December 2015
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	'''~~Unreleased structure~~'''		==NMR solution structure and assignments==
			<StructureSection load='2n8a' size='340' side='right' caption='[[2n8a]], [[NMR_Ensembles_of_Models \| 78 NMR models]]' scene=''>
	~~The entry~~ 2n8a is ~~ON HOLD~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2n8a]] is a 2 chain structure. 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>
	~~Authors~~: ~~Neuhaus~~, D., ~~Eustermann~~, S., ~~Yang~~, J., Wu, W.		</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>
			<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>
	~~Description~~:		<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]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			{{Large structure}}
			== 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>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Eustermann, S]]
			[[Category: Neuhaus, D]]
	[[Category: Wu, W]]		[[Category: Wu, W]]
	[[Category: Yang, J]]		[[Category: Yang, J]]
	[[Category: ~~Neuhaus, D]]~~		[[Category: Transferase]]
	~~[[Category: Eustermann, S~~]]

OCA: Protected "2n8a" [edit=sysop:move=sysop]

2015-10-15T22:08:52Z

Protected "2n8a" [edit=sysop:move=sysop]

← Older revision	Revision as of 22:08, 15 October 2015
(No difference)

OCA: New page: '''Unreleased structure''' The entry 2n8a is ON HOLD Authors: Neuhaus, D., Eustermann, S., Yang, J., Wu, W. Description: Category: Unreleased Structures Category: Wu, W [[Cate...

2015-10-15T22:08:51Z

New page: '''Unreleased structure''' The entry 2n8a is ON HOLD Authors: Neuhaus, D., Eustermann, S., Yang, J., Wu, W. Description: Category: Unreleased Structures Category: Wu, W [[Cate...

New page

'''Unreleased structure'''

The entry 2n8a is ON HOLD

Authors: Neuhaus, D., Eustermann, S., Yang, J., Wu, W.

Description:
[[Category: Unreleased Structures]]
[[Category: Wu, W]]
[[Category: Yang, J]]
[[Category: Neuhaus, D]]
[[Category: Eustermann, S]]