4a0d - Revision history

OCA at 07:36, 18 August 2022

OCA — Thu, 18 Aug 2022 07:36:36 GMT

←Older revision		Revision as of 07:36, 18 August 2022
Line 1:		Line 1:

	==Structure of unliganded human PARG catalytic domain==		==Structure of unliganded human PARG catalytic domain==
-	<StructureSection load='4a0d' size='340' side='right' caption='[[4a0d]], [[Resolution\|resolution]] 1.75Å' scene=''>	+	<StructureSection load='4a0d' size='340' side='right'caption='[[4a0d]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a0d]] 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=4A0D OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4A0D FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a0d]] is a 1 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=4A0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A0D FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</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" id="ligandDat"><scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Poly(ADP-ribose)_glycohydrolase Poly(ADP-ribose) glycohydrolase], with EC number [https://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=4a0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a0d OCA], [~~http~~://pdbe.org/4a0d PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4a0d RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4a0d PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4a0d 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=4a0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a0d OCA], [https://pdbe.org/4a0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a0d RCSB], [https://www.ebi.ac.uk/pdbsum/4a0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a0d 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 21:		Line 21:

	==See Also==		==See Also==
-	*[[Poly (ADP-ribose) glycohydrolase\|Poly (ADP-ribose) glycohydrolase]]	+	*[[Poly(ADP-ribose) glycohydrolase 3D structures\|Poly(ADP-ribose) glycohydrolase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Brassington, C]]		[[Category: Brassington, C]]
	[[Category: Ellston, J]]		[[Category: Ellston, J]]

OCA at 17:03, 27 February 2019

OCA — Wed, 27 Feb 2019 17:03:29 GMT

←Older revision		Revision as of 17:03, 27 February 2019
Line 31:		Line 31:
	[[Category: Hassall, G]]		[[Category: Hassall, G]]
	[[Category: Holdgate, G]]		[[Category: Holdgate, G]]
-	[[Category: ~~Mcalister~~, M]]	+	[[Category: McAlister, M]]
	[[Category: Overman, R]]		[[Category: Overman, R]]
	[[Category: Smith, G]]		[[Category: Smith, G]]

OCA at 09:31, 4 August 2016

OCA — Thu, 04 Aug 2016 09:31:14 GMT

←Older revision		Revision as of 09:31, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of unliganded human PARG catalytic domain==		==Structure of unliganded human PARG catalytic domain==
	<StructureSection load='4a0d' size='340' side='right' caption='[[4a0d]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='4a0d' size='340' side='right' caption='[[4a0d]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a0d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A0D FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a0d]] 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=4A0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A0D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</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=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</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='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=4a0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a0d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a0d RCSB], [http://www.ebi.ac.uk/pdbsum/4a0d PDBsum]</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=4a0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a0d OCA], [http://pdbe.org/4a0d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a0d RCSB], [http://www.ebi.ac.uk/pdbsum/4a0d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a0d ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4a0d" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Brassington, C]]		[[Category: Brassington, C]]
	[[Category: Ellston, J]]		[[Category: Ellston, J]]

OCA at 07:52, 25 December 2014

OCA — Thu, 25 Dec 2014 07:52:38 GMT

←Older revision		Revision as of 07:52, 25 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4a0d.~~png~~\|~~left\|200px~~]]	+	==Structure of unliganded human PARG catalytic domain==
		+	<StructureSection load='4a0d' size='340' side='right' caption='[[4a0d]], [[Resolution\|resolution]] 1.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4a0d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A0D FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a0d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a0d RCSB], [http://www.ebi.ac.uk/pdbsum/4a0d PDBsum]</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, thereby reversing the effects of poly(ADP-ribose) polymerases. PARG deficiency leads to cell death whilst PARG depletion causes sensitisation to certain DNA damaging agents, implicating PARG as a potential therapeutic target in several disease areas. Efforts to develop small molecule inhibitors of PARG activity have until recently been hampered by a lack of structural information on PARG. We have used a combination of bio-informatic and experimental approaches to engineer a crystallisable, catalytically active fragment of human PARG (hPARG). Here, we present high-resolution structures of the catalytic domain of hPARG in unliganded form and in complex with three inhibitors: ADP-ribose (ADPR), adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) and 8-n-octyl-amino-ADP-HPD. Our structures confirm conservation of overall fold amongst mammalian PARG glycohydrolase domains, whilst revealing additional flexible regions in the catalytic site. These new structures rationalise a body of published mutational data and the reported structure-activity relationship for ADP-HPD based PARG inhibitors. In addition, we have developed and used biochemical, isothermal titration calorimetry and surface plasmon resonance assays to characterise the binding of inhibitors to our PARG protein, thus providing a starting point for the design of new inhibitors.

-	~~{{STRUCTURE_4a0d\| PDB=4a0d \| SCENE= }}~~	+	Structures of the Human Poly (ADP-Ribose) Glycohydrolase Catalytic Domain Confirm Catalytic Mechanism and Explain Inhibition by ADP-HPD Derivatives.,Tucker JA, Bennett N, Brassington C, Durant ST, Hassall G, Holdgate G, McAlister M, Nissink JW, Truman C, Watson M PLoS One. 2012;7(12):e50889. doi: 10.1371/journal.pone.0050889. Epub 2012 Dec 10. PMID:23251397<ref>PMID:23251397</ref>

-	~~===Structure~~ of ~~unliganded human PARG catalytic domain===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_23251397}}~~	+	==See Also==
-		+	*[[Poly (ADP-ribose) glycohydrolase\|Poly (ADP-ribose) glycohydrolase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4a0d~~]] ~~is a 1 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A0D OCA].~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Brassington, C.]]	+	[[Category: Brassington, C]]
-	[[Category: Ellston, J.]]	+	[[Category: Ellston, J]]
-	[[Category: Hassall, G.]]	+	[[Category: Hassall, G]]
-	[[Category: Holdgate, G.]]	+	[[Category: Holdgate, G]]
-	[[Category: Mcalister, M.]]	+	[[Category: Mcalister, M]]
-	[[Category: Overman, R.]]	+	[[Category: Overman, R]]
-	[[Category: Smith, G.]]	+	[[Category: Smith, G]]
-	[[Category: Tucker, J A.]]	+	[[Category: Tucker, J A]]
-	[[Category: Watson, M.]]	+	[[Category: Watson, M]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 08:55, 16 January 2013

OCA — Wed, 16 Jan 2013 08:55:25 GMT

←Older revision		Revision as of 08:55, 16 January 2013
Line 5:		Line 5:
	===Structure of unliganded human PARG catalytic domain===		===Structure of unliganded human PARG catalytic domain===

		+	{{ABSTRACT_PUBMED_23251397}}

	==About this Structure==		==About this Structure==

OCA at 10:32, 19 December 2012

OCA — Wed, 19 Dec 2012 10:32:41 GMT

←Older revision		Revision as of 10:32, 19 December 2012
Line 1:		Line 1:
-	[[Image:4a0d.~~jpg~~\|left\|200px]]	+	[[Image:4a0d.png\|left\|200px]]

	{{STRUCTURE_4a0d\| PDB=4a0d \| SCENE= }}		{{STRUCTURE_4a0d\| PDB=4a0d \| SCENE= }}
Line 16:		Line 16:
	[[Category: Overman, R.]]		[[Category: Overman, R.]]
	[[Category: Smith, G.]]		[[Category: Smith, G.]]
-	[[Category: Tucker, J.]]	+	[[Category: Tucker, J A.]]
	[[Category: Watson, M.]]		[[Category: Watson, M.]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 07:09, 17 October 2012

OCA — Wed, 17 Oct 2012 07:09:14 GMT

←Older revision		Revision as of 07:09, 17 October 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4a0d.jpg\|left\|200px]]

-	~~The entry~~ 4a0d ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4a0d\| PDB=4a0d \| SCENE= }}

-	~~Authors: Brassington, C., Ellston, J., Hassall, G., Holdgate, G., McAlister, M., Overman, R., Smith, G., Tucker, J., Watson, M.~~	+	===Structure of unliganded human PARG catalytic domain===

-	~~Description:~~ Structure ~~of unliganded human PARG catalytic domain~~	+
		+	==About this Structure==
		+	[[4a0d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A0D OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Brassington, C.]]
		+	[[Category: Ellston, J.]]
		+	[[Category: Hassall, G.]]
		+	[[Category: Holdgate, G.]]
		+	[[Category: Mcalister, M.]]
		+	[[Category: Overman, R.]]
		+	[[Category: Smith, G.]]
		+	[[Category: Tucker, J.]]
		+	[[Category: Watson, M.]]
		+	[[Category: Hydrolase]]

OCA at 09:00, 30 October 2011

OCA — Sun, 30 Oct 2011 09:00:07 GMT

←Older revision		Revision as of 09:00, 30 October 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4a0d is ON HOLD	+	The entry 4a0d is ON HOLD until Paper Publication

	Authors: Brassington, C., Ellston, J., Hassall, G., Holdgate, G., McAlister, M., Overman, R., Smith, G., Tucker, J., Watson, M.		Authors: Brassington, C., Ellston, J., Hassall, G., Holdgate, G., McAlister, M., Overman, R., Smith, G., Tucker, J., Watson, M.

	Description: Structure of unliganded human PARG catalytic domain		Description: Structure of unliganded human PARG catalytic domain

OCA: Protected "4a0d" [edit=sysop:move=sysop]

OCA — Wed, 14 Sep 2011 06:10:33 GMT

Protected "4a0d" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:10, 14 September 2011

OCA: New page: '''Unreleased structure''' The entry 4a0d is ON HOLD Authors: Brassington, C., Ellston, J., Hassall, G., Holdgate, G., McAlister, M., Overman, R., Smith, G., Tucker, J., Watson, M. Des...

OCA — Wed, 14 Sep 2011 06:10:32 GMT

New page: '''Unreleased structure''' The entry 4a0d is ON HOLD Authors: Brassington, C., Ellston, J., Hassall, G., Holdgate, G., McAlister, M., Overman, R., Smith, G., Tucker, J., Watson, M. Des...

New page

'''Unreleased structure'''

The entry 4a0d is ON HOLD

Authors: Brassington, C., Ellston, J., Hassall, G., Holdgate, G., McAlister, M., Overman, R., Smith, G., Tucker, J., Watson, M.

Description: Structure of unliganded human PARG catalytic domain