7kk5 - Revision history

OCA at 15:26, 18 October 2023

OCA — Wed, 18 Oct 2023 15:26:33 GMT

←Older revision		Revision as of 15:26, 18 October 2023
Line 3:		Line 3:
	<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7kk5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kk5]] 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=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JD:2-{4-[(3S)-PIPERIDIN-3-YL]PHENYL}-2H-INDAZOLE-7-CARBOXAMIDE'>3JD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.7Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JD:2-{4-[(3S)-PIPERIDIN-3-YL]PHENYL}-2H-INDAZOLE-7-CARBOXAMIDE'>3JD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [https://pdbe.org/7kk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [https://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 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=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [https://pdbe.org/7kk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [https://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 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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	</div>		</div>
	<div class="pdbe-citations 7kk5" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7kk5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[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: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gajiwala~~, K S~~]]	+	[[Category: Gajiwala KS]]
-	[[Category: Ryan, K]]	+	[[Category: Ryan K]]
-	~~[[Category: Parp1]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:33, 28 April 2021

OCA — Wed, 28 Apr 2021 05:33:29 GMT

←Older revision		Revision as of 05:33, 28 April 2021
Line 3:		Line 3:
	<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7kk5]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kk5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JD:2-{4-[(3S)-PIPERIDIN-3-YL]PHENYL}-2H-INDAZOLE-7-CARBOXAMIDE'>3JD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JD:2-{4-[(3S)-PIPERIDIN-3-YL]PHENYL}-2H-INDAZOLE-7-CARBOXAMIDE'>3JD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [~~http~~://pdbe.org/7kk5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 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=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [https://pdbe.org/7kk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [https://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 ProSAT]</span></td></tr>
	</table>		</table>
	== 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 ==

OCA at 06:06, 20 January 2021

OCA — Wed, 20 Jan 2021 06:06:28 GMT

←Older revision		Revision as of 06:06, 20 January 2021
Line 1:		Line 1:

	==Structure of the catalytic domain of PARP1 in complex with niraparib==		==Structure of the catalytic domain of PARP1 in complex with niraparib==
-	<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]]' scene=''>	+	<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kk5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [http://pdbe.org/7kk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [http://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JD:2-{4-[(3S)-PIPERIDIN-3-YL]PHENYL}-2H-INDAZOLE-7-CARBOXAMIDE'>3JD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [http://pdbe.org/7kk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [http://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Poly ADP ribosyltransferases play a critical role in DNA repair and cell death, and PARP1 is a particularly important therapeutic target for the treatment of breast cancer due to its synthetic lethal relationship with BRCA1/2. Numerous PARP1 inhibitors have been developed, and their efficacy in cancer treatment is attributed to both the inhibition of enzymatic activity and their ability to trap PARP1 on to the damaged DNA, which is cytotoxic. Of the clinical PARP inhibitors, talazoparib is the most effective at trapping PARP1 on damaged DNA. Biochemically, talazoparib is also suspected to be a potent inhibitor of PARP5a/b (tankyrase1/2), which is an important regulator of Wnt/beta-catenin pathway. Here we show using competition experiments in cell lysate that, at a clinically relevant concentration, talazoparib can potentially bind and engage tankyrase1. Using surface plasmon resonance, we measured the dissociation constants of talazoparib, olaparib, niraparib and veliparib for their interaction with PARP1 and tankyrase1. The results show that talazoparib has strong affinity for PARP1 as well as uniquely strong affinity for tankyrase1. Finally, we used crystallography and hydrogen deuterium exchange mass spectroscopy to dissect the molecular mechanism of differential selectivity of these PARP1 inhibitors. From these data, we conclude that subtle differences between the ligand binding sites of PARP1 and tankyrase1, differences in the electrostatic nature of the ligands, protein dynamics, and ligand conformational energetics contribute to the different pharmacology of these PARP1 inhibitors. These results will help in the design of drugs to treat Wnt-beta-catenin pathway-related cancers, such as colorectal cancers.
		+
		+	Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1.,Ryan K, Bolanos B, Smith M, Palde P, Cuenca PD, VanArsdale TL, Niessen S, Zhang L, Behenna D, Ornelas MA, Tran KT, Kaiser S, Lum L, Stewart A, Gajiwala KS J Biol Chem. 2020 Dec 24. pii: RA120.016573. doi: 10.1074/jbc.RA120.016573. PMID:33361107<ref>PMID:33361107</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kk5" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gajiwala KS]]	+	[[Category: Gajiwala, K S]]
-	[[Category: Ryan K]]	+	[[Category: Ryan, K]]
		+	[[Category: Parp1]]
		+	[[Category: Transferase]]

OCA at 08:57, 6 January 2021

OCA — Wed, 06 Jan 2021 08:57:46 GMT

←Older revision		Revision as of 08:57, 6 January 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7kk5 ~~is ON HOLD until Paper Publication~~	+	==Structure of the catalytic domain of PARP1 in complex with niraparib==
-		+	<StructureSection load='7kk5' size='340' side='right'caption='[[7kk5]]' scene=''>
-	~~Authors~~: ~~Gajiwala~~, K.S., ~~Ryan~~, K.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KK5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KK5 FirstGlance]. <br>
-	~~Description: Structure of the catalytic domain of PARP1 in complex with niraparib~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kk5 OCA], [http://pdbe.org/7kk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kk5 RCSB], [http://www.ebi.ac.uk/pdbsum/7kk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kk5 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Ryan, K~~]]	+	__TOC__
-	[[Category: ~~Gajiwala,~~ K.S]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Gajiwala KS]]
		+	[[Category: Ryan K]]

OCA: Protected "7kk5" [edit=sysop:move=sysop]

OCA — Wed, 04 Nov 2020 05:40:26 GMT

Protected "7kk5" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:40, 4 November 2020

OCA: New page: '''Unreleased structure''' The entry 7kk5 is ON HOLD until Paper Publication Authors: Gajiwala, K.S., Ryan, K. Description: Structure of the catalytic domain of PARP1 in complex with n...

OCA — Wed, 04 Nov 2020 05:40:25 GMT

New page: '''Unreleased structure''' The entry 7kk5 is ON HOLD until Paper Publication Authors: Gajiwala, K.S., Ryan, K. Description: Structure of the catalytic domain of PARP1 in complex with n...

New page

'''Unreleased structure'''

The entry 7kk5 is ON HOLD until Paper Publication

Authors: Gajiwala, K.S., Ryan, K.

Description: Structure of the catalytic domain of PARP1 in complex with niraparib
[[Category: Unreleased Structures]]
[[Category: Ryan, K]]
[[Category: Gajiwala, K.S]]