6oal - Revision history

OCA at 07:06, 11 October 2023

2023-10-11T07:06:59Z

←Older revision		Revision as of 07:06, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6oal' size='340' side='right'caption='[[6oal]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6oal' size='340' side='right'caption='[[6oal]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6oal]] 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=6OAL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6OAL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6oal]] 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=6OAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OAL FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=M0P:1~~,~~3-dimethyl-8-{~~[~~2-(morpholin-4-yl)ethyl~~]~~sulfanyl}-3,7-dihydro-1H-purine-2,~~6~~-dione'>M0P</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]] 1.6Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=M0P:1,3-dimethyl-8-{[2-(morpholin-4-yl)ethyl]sulfanyl}-3,7-dihydro-1H-purine-2,6-dione'>M0P</scene></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat">[[6o9x\|6o9x]]~~, [~~[6o9y\|6o9y]], [[6oa0\|6oa0]], [[6oa1\|6oa1]], [[6oa3\|6oa3]], [[6oak\|6oak]]</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=6oal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oal OCA], [https://pdbe.org/6oal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oal RCSB], [https://www.ebi.ac.uk/pdbsum/6oal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oal ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6oal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oal OCA], [~~http~~://pdbe.org/6oal PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6oal RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6oal PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6oal 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 ==
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	</div>		</div>
	<div class="pdbe-citations 6oal" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6oal" 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: Ahmed, Z]]	+	[[Category: Ahmed Z]]
-	[[Category: Brosey~~, C A~~]]	+	[[Category: Brosey CA]]
-	[[Category: Tainer~~, J A~~]]	+	[[Category: Tainer JA]]
-	[[Category: Warden, S]]	+	[[Category: Warden S]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 07:19, 27 May 2020

2020-05-27T07:19:05Z

←Older revision		Revision as of 07:19, 27 May 2020
Line 3:		Line 3:
	<StructureSection load='6oal' size='340' side='right'caption='[[6oal]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6oal' size='340' side='right'caption='[[6oal]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6oal]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OAL OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6OAL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6oal]] 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=6OAL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OAL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M0P:1,3-dimethyl-8-{[2-(morpholin-4-yl)ethyl]sulfanyl}-3,7-dihydro-1H-purine-2,6-dione'>M0P</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M0P:1,3-dimethyl-8-{[2-(morpholin-4-yl)ethyl]sulfanyl}-3,7-dihydro-1H-purine-2,6-dione'>M0P</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o9x\|6o9x]], [[6o9y\|6o9y]], [[6oa0\|6oa0]], [[6oa1\|6oa1]], [[6oa3\|6oa3]], [[6oak\|6oak]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o9x\|6o9x]], [[6o9y\|6o9y]], [[6oa0\|6oa0]], [[6oa1\|6oa1]], [[6oa3\|6oa3]], [[6oak\|6oak]]</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=6oal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oal OCA], [http://pdbe.org/6oal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oal RCSB], [http://www.ebi.ac.uk/pdbsum/6oal PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oal ProSAT]</span></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=6oal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oal OCA], [http://pdbe.org/6oal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oal RCSB], [http://www.ebi.ac.uk/pdbsum/6oal PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oal 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>		[[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 ==
		+	Poly(ADP-ribose)ylation (PARylation) by PAR polymerase 1 (PARP1) and PARylation removal by poly(ADP-ribose) glycohydrolase (PARG) critically regulate DNA damage responses; yet, conflicting reports obscure PARG biology and its impact on cancer cell resistance to PARP1 inhibitors. Here, we found that PARG expression is upregulated in many cancers. We employed chemical library screening to identify and optimize methylxanthine derivatives as selective bioavailable PARG inhibitors. Multiple crystal structures reveal how substituent positions on the methylxanthine core dictate binding modes and inducible-complementarity with a PARG-specific tyrosine clasp and arginine switch, supporting inhibitor specificity and a competitive inhibition mechanism. Cell-based assays show selective PARG inhibition and PARP1 hyperPARylation. Moreover, our PARG inhibitor sensitizes cells to radiation-induced DNA damage, suppresses replication fork progression and impedes cancer cell survival. In PARP inhibitor-resistant A172 glioblastoma cells, our PARG inhibitor shows comparable killing to Nedaplatin, providing further proof-of-concept that selectively inhibiting PARG can impair cancer cell survival.
		+
		+	Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death.,Houl JH, Ye Z, Brosey CA, Balapiti-Modarage LPF, Namjoshi S, Bacolla A, Laverty D, Walker BL, Pourfarjam Y, Warden LS, Babu Chinnam N, Moiani D, Stegeman RA, Chen MK, Hung MC, Nagel ZD, Ellenberger T, Kim IK, Jones DE, Ahmed Z, Tainer JA Nat Commun. 2019 Dec 11;10(1):5654. doi: 10.1038/s41467-019-13508-4. PMID:31827085<ref>PMID:31827085</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6oal" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Ahmed, Z]]		[[Category: Ahmed, Z]]

OCA at 09:43, 18 March 2020

2020-03-18T09:43:19Z

←Older revision		Revision as of 09:43, 18 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6oal is ~~ON HOLD until Paper Publication~~	+	==Structure of human PARG complexed with JA2120==
-		+	<StructureSection load='6oal' size='340' side='right'caption='[[6oal]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6oal]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OAL FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M0P:1,3-dimethyl-8-{[2-(morpholin-4-yl)ethyl]sulfanyl}-3,7-dihydro-1H-purine-2,6-dione'>M0P</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6o9x\|6o9x]], [[6o9y\|6o9y]], [[6oa0\|6oa0]], [[6oa1\|6oa1]], [[6oa3\|6oa3]], [[6oak\|6oak]]</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=6oal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oal OCA], [http://pdbe.org/6oal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oal RCSB], [http://www.ebi.ac.uk/pdbsum/6oal PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oal 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: Large Structures]]
		+	[[Category: Ahmed, Z]]
		+	[[Category: Brosey, C A]]
		+	[[Category: Tainer, J A]]
		+	[[Category: Warden, S]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

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

2019-03-27T05:03:06Z

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

←Older revision

Revision as of 05:03, 27 March 2019

OCA: New page: '''Unreleased structure''' The entry 6oal is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2019-03-27T05:03:04Z

New page: '''Unreleased structure''' The entry 6oal is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6oal is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]