6hmn - Revision history

OCA at 11:33, 24 January 2024

OCA — Wed, 24 Jan 2024 11:33:06 GMT

←Older revision		Revision as of 11:33, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6hmn' size='340' side='right'caption='[[6hmn]], [[Resolution\|resolution]] 2.87Å' scene=''>		<StructureSection load='6hmn' size='340' side='right'caption='[[6hmn]], [[Resolution\|resolution]] 2.87Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hmn]] 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=6HMN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6HMN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hmn]] 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=6HMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HMN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70J:3-methyl-6-[[(1-methylcyclopropyl)amino]-bis(oxidanyl)-$l^{4}-sulfanyl]-1-(phenylmethyl)quinazoline-2,4-dione'>70J</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.87Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PARG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=70J:3-methyl-6-[[(1-methylcyclopropyl)amino]-bis(oxidanyl)-$l^{4}-sulfanyl]-1-(phenylmethyl)quinazoline-2,4-dione'>70J</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Poly(ADP-ribose)_glycohydrolase Poly(ADP-ribose) glycohydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.143 3.2.1.143] </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=6hmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmn OCA], [https://pdbe.org/6hmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hmn RCSB], [https://www.ebi.ac.uk/pdbsum/6hmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmn 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=6hmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmn OCA], [~~http~~://pdbe.org/6hmn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6hmn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6hmn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmn ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PARG_HUMAN PARG_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers. Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters.<ref>PMID:23102699</ref>	+	[https://www.uniprot.org/uniprot/PARG_HUMAN PARG_HUMAN] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers. Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters.<ref>PMID:23102699</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6hmn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6hmn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly(ADP-ribose) glycohydrolase 3D structures\|Poly(ADP-ribose) glycohydrolase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brassington, C]]	+	[[Category: Brassington C]]
-	[[Category: Hassall, G]]	+	[[Category: Hassall G]]
-	[[Category: Tucker~~, J A]]~~	+	[[Category: Tucker JA]]
-	~~[[Category: Competitive inhibitor]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 07:58, 24 April 2019

OCA — Wed, 24 Apr 2019 07:58:07 GMT

←Older revision		Revision as of 07:58, 24 April 2019
Line 1:		Line 1:

	==POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH PDD00014909==		==POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH PDD00014909==
-	<StructureSection load='6hmn' size='340' side='right' caption='[[6hmn]], [[Resolution\|resolution]] 2.87Å' scene=''>	+	<StructureSection load='6hmn' size='340' side='right'caption='[[6hmn]], [[Resolution\|resolution]] 2.87Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hmn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HMN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HMN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hmn]] 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=6HMN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HMN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70J:3-methyl-6-[[(1-methylcyclopropyl)amino]-bis(oxidanyl)-$l^{4}-sulfanyl]-1-(phenylmethyl)quinazoline-2,4-dione'>70J</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70J:3-methyl-6-[[(1-methylcyclopropyl)amino]-bis(oxidanyl)-$l^{4}-sulfanyl]-1-(phenylmethyl)quinazoline-2,4-dione'>70J</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">PARG ([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/Poly(ADP-ribose)_glycohydrolase Poly(ADP-ribose) glycohydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.143 3.2.1.143] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Poly(ADP-ribose)_glycohydrolase Poly(ADP-ribose) glycohydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.143 3.2.1.143] </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=6hmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmn OCA], [http://pdbe.org/6hmn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hmn RCSB], [http://www.ebi.ac.uk/pdbsum/6hmn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmn 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=6hmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmn OCA], [http://pdbe.org/6hmn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hmn RCSB], [http://www.ebi.ac.uk/pdbsum/6hmn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmn ProSAT]</span></td></tr>
Line 10:		Line 11:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PARG_HUMAN PARG_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers. Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters.<ref>PMID:23102699</ref>		[[http://www.uniprot.org/uniprot/PARG_HUMAN PARG_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers. Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters.<ref>PMID:23102699</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors.
		+
		+	Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides.,Waszkowycz B, Smith KM, McGonagle AE, Jordan AM, Acton B, Fairweather EE, Griffiths LA, Hamilton NM, Hamilton NS, Hitchin JR, Hutton CP, James DI, Jones CD, Jones S, Mould DP, Small HF, Stowell AIJ, Tucker JA, Waddell ID, Ogilvie DJ J Med Chem. 2018 Dec 13;61(23):10767-10792. doi: 10.1021/acs.jmedchem.8b01407., Epub 2018 Nov 19. PMID:30403352<ref>PMID:30403352</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6hmn" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Brassington, C]]		[[Category: Brassington, C]]
	[[Category: Hassall, G]]		[[Category: Hassall, G]]

OCA at 08:20, 14 November 2018

OCA — Wed, 14 Nov 2018 08:20:46 GMT

←Older revision		Revision as of 08:20, 14 November 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6hmn is ~~ON HOLD until Paper Publication~~	+	==POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH PDD00014909==
-		+	<StructureSection load='6hmn' size='340' side='right' caption='[[6hmn]], [[Resolution\|resolution]] 2.87Å' scene=''>
-	~~Authors~~: ~~Tucker~~, J.A., ~~Brassington~~, C., ~~Hassall~~, G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6hmn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HMN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HMN FirstGlance]. <br>
-	~~Description: POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH PDD00014909~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70J:3-methyl-6-[[(1-methylcyclopropyl)amino]-bis(oxidanyl)-$l^{4}-sulfanyl]-1-(phenylmethyl)quinazoline-2,4-dione'>70J</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Poly(ADP-ribose)_glycohydrolase Poly(ADP-ribose) glycohydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.143 3.2.1.143] </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=6hmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmn OCA], [http://pdbe.org/6hmn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hmn RCSB], [http://www.ebi.ac.uk/pdbsum/6hmn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmn ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PARG_HUMAN PARG_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers. Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters.<ref>PMID:23102699</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Brassington, C]]		[[Category: Brassington, C]]
	[[Category: Hassall, G]]		[[Category: Hassall, G]]
-	[[Category: Tucker, J.A]]	+	[[Category: Tucker, J A]]
		+	[[Category: Competitive inhibitor]]
		+	[[Category: Hydrolase]]

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

OCA — Wed, 19 Sep 2018 18:14:22 GMT

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

←Older revision

Revision as of 18:14, 19 September 2018

OCA: New page: '''Unreleased structure''' The entry 6hmn is ON HOLD until Paper Publication Authors: Tucker, J.A., Brassington, C., Hassall, G. Description: POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH...

OCA — Wed, 19 Sep 2018 18:14:21 GMT

New page: '''Unreleased structure''' The entry 6hmn is ON HOLD until Paper Publication Authors: Tucker, J.A., Brassington, C., Hassall, G. Description: POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH...

New page

'''Unreleased structure'''

The entry 6hmn is ON HOLD until Paper Publication

Authors: Tucker, J.A., Brassington, C., Hassall, G.

Description: POLYADPRIBOSYL GLYCOSIDASE IN COMPLEX WITH PDD00014909
[[Category: Unreleased Structures]]
[[Category: Brassington, C]]
[[Category: Hassall, G]]
[[Category: Tucker, J.A]]