6nrg - Revision history

OCA at 06:58, 11 October 2023

OCA — Wed, 11 Oct 2023 06:58:28 GMT

←Older revision		Revision as of 06:58, 11 October 2023
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	<StructureSection load='6nrg' size='340' side='right'caption='[[6nrg]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='6nrg' size='340' side='right'caption='[[6nrg]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nrg]] is a 1 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=6NRG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NRG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nrg]] 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=6NRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NRG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=KYY:2-{[3-fluoro-4-(1H-tetrazol-5-yl)phenyl]methyl}-3-hydroxy-1-benzofuran-7-carboxamide'>KYY</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nrf\|6nrf]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=KYY:2-{[3-fluoro-4-(1H-tetrazol-5-yl)phenyl]methyl}-3-hydroxy-1-benzofuran-7-carboxamide'>KYY</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'>[https://proteopedia.org/fgij/fg.htm?mol=6nrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrg OCA], [https://pdbe.org/6nrg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nrg RCSB], [https://www.ebi.ac.uk/pdbsum/6nrg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrg 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=6nrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrg OCA], [~~http~~://pdbe.org/6nrg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nrg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nrg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrg 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Langelier~~, M F~~]]	+	[[Category: Langelier MF]]
-	[[Category: Pascal~~, J M]]~~	+	[[Category: Pascal JM]]
-	~~[[Category: Artd1]]~~	+
-	~~[[Category: Parp inhibitor]]~~	+
-	~~[[Category: Parp-1]]~~	+
-	~~[[Category: Parp1]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:23, 8 January 2020

OCA — Wed, 08 Jan 2020 09:23:09 GMT

←Older revision		Revision as of 09:23, 8 January 2020
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	<StructureSection load='6nrg' size='340' side='right'caption='[[6nrg]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='6nrg' size='340' side='right'caption='[[6nrg]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nrg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NRG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nrg]] is a 1 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=6NRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NRG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=KYY:2-{[3-fluoro-4-(1H-tetrazol-5-yl)phenyl]methyl}-3-hydroxy-1-benzofuran-7-carboxamide'>KYY</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"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=KYY:2-{[3-fluoro-4-(1H-tetrazol-5-yl)phenyl]methyl}-3-hydroxy-1-benzofuran-7-carboxamide'>KYY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nrf\|6nrf]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nrf\|6nrf]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrg OCA], [http://pdbe.org/6nrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nrg RCSB], [http://www.ebi.ac.uk/pdbsum/6nrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrg 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=6nrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrg OCA], [http://pdbe.org/6nrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nrg RCSB], [http://www.ebi.ac.uk/pdbsum/6nrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrg ProSAT]</span></td></tr>
	</table>		</table>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6nrg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nrg" 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: Large Structures]]		[[Category: Large Structures]]
	[[Category: Langelier, M F]]		[[Category: Langelier, M F]]

OCA at 16:40, 14 August 2019

OCA — Wed, 14 Aug 2019 16:40:29 GMT

←Older revision		Revision as of 16:40, 14 August 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nrg is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT57==
		+	<StructureSection load='6nrg' size='340' side='right'caption='[[6nrg]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6nrg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NRG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=KYY:2-{[3-fluoro-4-(1H-tetrazol-5-yl)phenyl]methyl}-3-hydroxy-1-benzofuran-7-carboxamide'>KYY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nrf\|6nrf]]</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=6nrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrg OCA], [http://pdbe.org/6nrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nrg RCSB], [http://www.ebi.ac.uk/pdbsum/6nrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrg ProSAT]</span></td></tr>
		+	</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(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors are a class of anticancer drugs that block the catalytic activity of PARP proteins. Optimization of our lead compound 1 (( Z)-2-benzylidene-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC50 = 434 nM) led to a tetrazolyl analogue (51, IC50 = 35 nM) with improved inhibition. Isosteric replacement of the tetrazole ring with a carboxyl group (60, IC50 = 68 nM) gave a promising new lead, which was subsequently optimized to obtain analogues with potent PARP-1 IC50 values (4-197 nM). PARP enzyme profiling revealed that the majority of compounds are selective toward PARP-2 with IC50 values comparable to clinical inhibitors. X-ray crystal structures of the key inhibitors bound to PARP-1 illustrated the mode of interaction with analogue appendages extending toward the PARP-1 adenosine-binding pocket. Compound 81, an isoform-selective PARP-1/-2 (IC50 = 30 nM/2 nM) inhibitor, demonstrated selective cytotoxic effect toward breast cancer gene 1 ( BRCA1)-deficient cells compared to isogenic BRCA1-proficient cells.

-	~~Authors~~:	+	Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity.,Velagapudi UK, Langelier MF, Delgado-Martin C, Diolaiti ME, Bakker S, Ashworth A, Patel BA, Shao X, Pascal JM, Talele TT J Med Chem. 2019 Jun 13;62(11):5330-5357. doi: 10.1021/acs.jmedchem.8b01709. Epub, 2019 May 24. PMID:31042381<ref>PMID:31042381</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6nrg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Langelier, M F]]
		+	[[Category: Pascal, J M]]
		+	[[Category: Artd1]]
		+	[[Category: Parp inhibitor]]
		+	[[Category: Parp-1]]
		+	[[Category: Parp1]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:38, 13 February 2019

OCA — Wed, 13 Feb 2019 07:38:57 GMT

←Older revision		Revision as of 07:38, 13 February 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 30 Jan 2019 06:48:51 GMT

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

←Older revision

Revision as of 06:48, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6nrg is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 30 Jan 2019 06:48:50 GMT

New page: '''Unreleased structure''' The entry 6nrg is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6nrg is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]