7l9f - Revision history

OCA at 15:41, 18 October 2023

OCA — Wed, 18 Oct 2023 15:41:20 GMT

←Older revision		Revision as of 15:41, 18 October 2023
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	<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7l9f]] is a 4 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=7L9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L9F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7l9f]] 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=7L9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L9F 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=CA:CALCIUM+ION'>CA</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]] 1.75Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADPRHL2, ARH3 ([https://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=CA:CALCIUM+ION'>CA</scene></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=7l9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l9f OCA], [https://pdbe.org/7l9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l9f RCSB], [https://www.ebi.ac.uk/pdbsum/7l9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l9f 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=7l9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l9f OCA], [https://pdbe.org/7l9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l9f RCSB], [https://www.ebi.ac.uk/pdbsum/7l9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l9f 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 ==
-	[[https://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 ==
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	</div>		</div>
	<div class="pdbe-citations 7l9f" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7l9f" 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: Kim~~, I K~~]]	+	[[Category: Kim IK]]
-	[[Category: Kurinov, I]]	+	[[Category: Kurinov I]]
-	[[Category: Moss, J]]	+	[[Category: Moss J]]
-	[[Category: Pourfarjam, Y]]	+	[[Category: Pourfarjam Y]]
-	~~[[Category: Adp-ribose]]~~	+
-	~~[[Category: Calcium]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 09:40, 12 May 2021

OCA — Wed, 12 May 2021 09:40:40 GMT

←Older revision		Revision as of 09:40, 12 May 2021
Line 1:		Line 1:

	==Crystal structure of human ARH3 bound to calcium and ADP-ribose==		==Crystal structure of human ARH3 bound to calcium and ADP-ribose==
-	<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]]' scene=''>	+	<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L9F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7l9f]] is a 4 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=7L9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L9F FirstGlance]. <br>
-	</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=7l9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l9f OCA], [https://pdbe.org/7l9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l9f RCSB], [https://www.ebi.ac.uk/pdbsum/7l9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l9f ProSAT]</span></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=CA:CALCIUM+ION'>CA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADPRHL2, ARH3 ([https://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=7l9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l9f OCA], [https://pdbe.org/7l9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l9f RCSB], [https://www.ebi.ac.uk/pdbsum/7l9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l9f ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://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-ribosylation is a reversible and site-specific post-translational modification that regulates a wide array of cellular signaling pathways. Regulation of ADP-ribosylation is vital for maintaining genomic integrity and uncontrolled accumulation of poly(ADP-ribosyl)ation triggers a poly(ADP-ribose) (PAR)-dependent release of apoptosis-inducing factor from mitochondria, leading to cell death. ADP-ribosyl-acceptor hydrolase 3 (ARH3) cleaves PAR and mono(ADP-ribosyl)ation at serine following DNA damage. ARH3 is also a metalloenzyme with strong metal selectivity. While coordination of two magnesium ions (Mg(A) and Mg(B)) significantly enhances its catalytic efficiency, calcium binding suppresses its function. However, how the coordination of different metal ions affects its catalysis has not been defined. Here we report a new crystal structure of ARH3 complexed with its product ADP-ribose and calcium. This structure shows that calcium coordination significantly distorts the binuclear metal center of ARH3, which results in decreased binding affinity to ADP-ribose, and suboptimal substrate alignment, leading to impaired hydrolysis of PAR and mono(ADP-ribosyl)ated serines. Furthermore, combined structural and mutational analysis of the metal-coordinating acidic residues revealed that Mg(A) is crucial for optimal substrate positioning for catalysis, whereas Mg(B) plays a key role in substrate binding. Our collective data provide novel insights into the different roles of these metal ions and the basis of metal selectivity of ARH3, and contribute to understanding the dynamic regulation of cellular ADP-ribosylations during the DNA damage response.
		+
		+	Structural and biochemical analysis of human ADP-ribosyl-acceptor hydrolase 3 (ARH3) reveals the basis of metal selectivity and different roles for the two Mg ions.,Pourfarjam Y, Ma Z, Kurinov I, Moss J, Kim IK J Biol Chem. 2021 Apr 21:100692. doi: 10.1016/j.jbc.2021.100692. PMID:33894202<ref>PMID:33894202</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7l9f" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kim IK]]	+	[[Category: Kim, I K]]
-	[[Category: Kurinov I]]	+	[[Category: Kurinov, I]]
-	[[Category: Moss J]]	+	[[Category: Moss, J]]
-	[[Category: Pourfarjam Y]]	+	[[Category: Pourfarjam, Y]]
		+	[[Category: Adp-ribose]]
		+	[[Category: Calcium]]
		+	[[Category: Hydrolase]]

OCA at 05:21, 28 April 2021

OCA — Wed, 28 Apr 2021 05:21:55 GMT

←Older revision		Revision as of 05:21, 28 April 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7l9f is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human ARH3 bound to calcium and ADP-ribose==
-		+	<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7L9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L9F FirstGlance]. <br>
-	~~Description~~:	+	</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=7l9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l9f OCA], [https://pdbe.org/7l9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l9f RCSB], [https://www.ebi.ac.uk/pdbsum/7l9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l9f ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Kim IK]]
		+	[[Category: Kurinov I]]
		+	[[Category: Moss J]]
		+	[[Category: Pourfarjam Y]]

OCA: Protected "7l9f" [edit=sysop:move=sysop]

OCA — Wed, 10 Feb 2021 09:14:46 GMT

Protected "7l9f" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:14, 10 February 2021

OCA: New page: '''Unreleased structure''' The entry 7l9f is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 10 Feb 2021 09:14:45 GMT

New page: '''Unreleased structure''' The entry 7l9f is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7l9f is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]