6d36 - Revision history

OCA at 15:17, 4 October 2023

2023-10-04T15:17:02Z

←Older revision		Revision as of 15:17, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6d36' size='340' side='right'caption='[[6d36]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='6d36' size='340' side='right'caption='[[6d36]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d36]] is a 4 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=6D36 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6D36 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d36]] 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=6D36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D36 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADPRHL2, ARH3 ([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=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6d36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d36 OCA], [https://pdbe.org/6d36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d36 RCSB], [https://www.ebi.ac.uk/pdbsum/6d36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d36 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=6d36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d36 OCA], [~~http~~://pdbe.org/6d36 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6d36 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6d36 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6d36 ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/ADPRS_HUMAN ADPRS_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~ARHL2_HUMAN ARHL2_HUMAN~~]~~] Poly(~~ADP-ribose~~) synthesized after DNA damage is only present transiently~~ and ~~is rapidly degraded by~~ poly(ADP-ribose) ~~glycohydrolase. Poly(~~ADP-ribose) ~~metabolism may be required for maintenance of the normal function of neuronal cells~~. ~~Generates~~ ADP-~~ribose from poly~~-(ADP-ribose), ~~but does~~ not hydrolyze ADP-~~ribose~~-arginine, -cysteine, -diphthamide, or -asparagine bonds. ~~Due~~ to ~~catalytic inactivity of PARG mitochondrial isoforms~~, ~~ARH3~~ is ~~the only PAR hydrolyzing enzyme~~ in mitochondria.<ref>PMID:16278211</ref>	+	[https://www.uniprot.org/uniprot/ADPRS_HUMAN ADPRS_HUMAN] ADP-ribose glycohydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:30045870, PubMed:29907568, PubMed:30401461, PubMed:33186521). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885).<ref>PMID:16278211</ref> <ref>PMID:17075046</ref> <ref>PMID:21498885</ref> <ref>PMID:22433848</ref> <ref>PMID:28650317</ref> <ref>PMID:29234005</ref> <ref>PMID:29480802</ref> <ref>PMID:29907568</ref> <ref>PMID:30045870</ref> <ref>PMID:30401461</ref> <ref>PMID:33186521</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kim~~, I K~~]]	+	[[Category: Kim IK]]
-	[[Category: Kurinov, I]]	+	[[Category: Kurinov I]]
-	[[Category: Pourfarjam, Y]]	+	[[Category: Pourfarjam Y]]
-	[[Category: Ventura, J]]	+	[[Category: Ventura J]]
-	~~[[Category: Hydrolase~~]]	+

OCA at 09:03, 11 November 2020

2020-11-11T09:03:41Z

←Older revision		Revision as of 09:03, 11 November 2020
Line 1:		Line 1:

	==Structure of human ARH3 bound to ADP-ribose and magnesium==		==Structure of human ARH3 bound to ADP-ribose and magnesium==
-	<StructureSection load='6d36' size='340' side='right' caption='[[6d36]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='6d36' size='340' side='right'caption='[[6d36]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d36]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D36 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6D36 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d36]] is a 4 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=6D36 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D36 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADPRHL2, ARH3 ([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=6d36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d36 OCA], [http://pdbe.org/6d36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d36 RCSB], [http://www.ebi.ac.uk/pdbsum/6d36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d36 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=6d36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d36 OCA], [http://pdbe.org/6d36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d36 RCSB], [http://www.ebi.ac.uk/pdbsum/6d36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d36 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ARHL2_HUMAN ARHL2_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. Poly(ADP-ribose) metabolism may be required for maintenance of the normal function of neuronal cells. Generates ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds. Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3 is the only PAR hydrolyzing enzyme in mitochondria.<ref>PMID:16278211</ref>		[[http://www.uniprot.org/uniprot/ARHL2_HUMAN ARHL2_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. Poly(ADP-ribose) metabolism may be required for maintenance of the normal function of neuronal cells. Generates ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds. Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3 is the only PAR hydrolyzing enzyme in mitochondria.<ref>PMID:16278211</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	ADP-ribosyl-acceptor hydrolase 3 (ARH3) plays important roles in regulation of poly(ADP-ribosyl)ation, a reversible post-translational modification, and in maintenance of genomic integrity. ARH3 degrades poly(ADP-ribose) to protect cells from poly(ADP-ribose)-dependent cell death, reverses serine mono(ADP-ribosyl)ation, and hydrolyzes O-acetyl-ADP-ribose, a product of Sirtuin-catalyzed histone deacetylation. ARH3 preferentially hydrolyzes O-linkages attached to the anomeric C1'' of ADP-ribose; however, how ARH3 specifically recognizes and cleaves structurally diverse substrates remains unknown. Here, structures of full-length human ARH3 bound to ADP-ribose and Mg(2+), coupled with computational modeling, reveal a dramatic conformational switch from closed to open states that enables specific substrate recognition. The glutamate flap, which blocks substrate entrance to Mg(2+) in the unliganded closed state, is ejected from the active site when substrate is bound. This closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2''- and 3''-hydroxyls of ADP-ribose. Our collective data uncover an unprecedented structural plasticity of ARH3 that supports its specificity for the 1''-O-linkage in substrates and Mg(2+)-dependent catalysis.
		+
		+	Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition.,Pourfarjam Y, Ventura J, Kurinov I, Cho A, Moss J, Kim IK J Biol Chem. 2018 Aug 10;293(32):12350-12359. doi: 10.1074/jbc.RA118.003586. Epub, 2018 Jun 15. PMID:29907568<ref>PMID:29907568</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6d36" 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: Large Structures]]
	[[Category: Kim, I K]]		[[Category: Kim, I K]]
	[[Category: Kurinov, I]]		[[Category: Kurinov, I]]

OCA at 05:52, 20 June 2018

2018-06-20T05:52:21Z

←Older revision		Revision as of 05:52, 20 June 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6d36 is ~~ON HOLD~~	+	==Structure of human ARH3 bound to ADP-ribose and magnesium==
-		+	<StructureSection load='6d36' size='340' side='right' caption='[[6d36]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6d36]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D36 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6d36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d36 OCA], [http://pdbe.org/6d36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d36 RCSB], [http://www.ebi.ac.uk/pdbsum/6d36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d36 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ARHL2_HUMAN ARHL2_HUMAN]] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. Poly(ADP-ribose) metabolism may be required for maintenance of the normal function of neuronal cells. Generates ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds. Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3 is the only PAR hydrolyzing enzyme in mitochondria.<ref>PMID:16278211</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kim, I K]]
		+	[[Category: Kurinov, I]]
		+	[[Category: Pourfarjam, Y]]
		+	[[Category: Ventura, J]]
		+	[[Category: Hydrolase]]

OCA: Protected "6d36" [edit=sysop:move=sysop]

2018-04-25T04:08:01Z

Protected "6d36" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:08, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 6d36 is ON HOLD Authors: Description: Category: Unreleased Structures

2018-04-25T04:08:00Z

New page: '''Unreleased structure''' The entry 6d36 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6d36 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]