6vkk - Revision history

OCA at 08:14, 11 October 2023

OCA — Wed, 11 Oct 2023 08:14:27 GMT

←Older revision		Revision as of 08:14, 11 October 2023
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	==Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib==		==Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib==
-	<StructureSection load='6vkk' size='340' side='right'caption='[[6vkk]]' scene=''>	+	<StructureSection load='6vkk' size='340' side='right'caption='[[6vkk]], [[Resolution\|resolution]] 2.10Å' 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=6VKK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VKK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vkk]] 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=6VKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VKK 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=6vkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vkk OCA], [~~http~~://pdbe.org/6vkk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vkk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vkk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vkk ProSAT]</span></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]] 2.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RPB:RUCAPARIB'>RPB</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=6vkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vkk OCA], [https://pdbe.org/6vkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vkk RCSB], [https://www.ebi.ac.uk/pdbsum/6vkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vkk ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. Although different forms of PARPi all target the catalytic center of the enzyme, they have variable abilities to trap PARP-1. We found that several structurally distinct PARPi drive PARP-1 allostery to promote release from a DNA break. Other inhibitors drive allostery to retain PARP-1 on a DNA break. Further, we generated a new PARPi compound, converting an allosteric pro-release compound to a pro-retention compound and increasing its ability to kill cancer cells. These developments are pertinent to clinical applications where PARP-1 trapping is either desirable or undesirable.
		+
		+	Structural basis for allosteric PARP-1 retention on DNA breaks.,Zandarashvili L, Langelier MF, Velagapudi UK, Hancock MA, Steffen JD, Billur R, Hannan ZM, Wicks AJ, Krastev DB, Pettitt SJ, Lord CJ, Talele TT, Pascal JM, Black BE Science. 2020 Apr 3;368(6486). pii: 368/6486/eaax6367. doi:, 10.1126/science.aax6367. PMID:32241924<ref>PMID:32241924</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vkk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Pascal JM]]		[[Category: Pascal JM]]
	[[Category: Steffen JD]]		[[Category: Steffen JD]]

OCA at 10:13, 17 June 2020

OCA — Wed, 17 Jun 2020 10:13:44 GMT

←Older revision		Revision as of 10:13, 17 June 2020
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-	'''Unreleased structure'''

-	~~The entry 6vkk is ON HOLD until Paper Publication~~	+	==Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib==
-		+	<StructureSection load='6vkk' size='340' side='right'caption='[[6vkk]]' scene=''>
-	~~Authors: Steffen, J.D., Pascal, J.M.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VKK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VKK FirstGlance]. <br>
-	~~Description:~~ Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib	+	</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=6vkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vkk OCA], [http://pdbe.org/6vkk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vkk RCSB], [http://www.ebi.ac.uk/pdbsum/6vkk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vkk ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Pascal~~, J.M~~]]	+	__TOC__
-	[[Category: Steffen~~, J.D~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Pascal JM]]
		+	[[Category: Steffen JD]]

OCA at 03:51, 13 May 2020

OCA — Wed, 13 May 2020 03:51:57 GMT

←Older revision		Revision as of 03:51, 13 May 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6vkk is ON HOLD	+	The entry 6vkk is ON HOLD until Paper Publication

	Authors: Steffen, J.D., Pascal, J.M.		Authors: Steffen, J.D., Pascal, J.M.

OCA: Protected "6vkk" [edit=sysop:move=sysop]

OCA — Wed, 29 Jan 2020 13:38:14 GMT

Protected "6vkk" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:38, 29 January 2020

OCA: New page: '''Unreleased structure''' The entry 6vkk is ON HOLD Authors: Steffen, J.D., Pascal, J.M. Description: Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib [[Categ...

OCA — Wed, 29 Jan 2020 13:38:12 GMT

New page: '''Unreleased structure''' The entry 6vkk is ON HOLD Authors: Steffen, J.D., Pascal, J.M. Description: Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib [[Categ...

New page

'''Unreleased structure'''

The entry 6vkk is ON HOLD

Authors: Steffen, J.D., Pascal, J.M.

Description: Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib
[[Category: Unreleased Structures]]
[[Category: Pascal, J.M]]
[[Category: Steffen, J.D]]