7l9f

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==Crystal structure of human ARH3 bound to calcium and ADP-ribose==
==Crystal structure of human ARH3 bound to calcium and ADP-ribose==
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<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]]' scene=''>
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<StructureSection load='7l9f' size='340' side='right'caption='[[7l9f]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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>
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<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>
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</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>
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</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>
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<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>
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<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>
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== Function ==
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[[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7l9f" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Kim IK]]
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[[Category: Kim, I K]]
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[[Category: Kurinov I]]
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[[Category: Kurinov, I]]
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[[Category: Moss J]]
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[[Category: Moss, J]]
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[[Category: Pourfarjam Y]]
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[[Category: Pourfarjam, Y]]
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[[Category: Adp-ribose]]
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[[Category: Calcium]]
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[[Category: Hydrolase]]

Revision as of 09:40, 12 May 2021

Crystal structure of human ARH3 bound to calcium and ADP-ribose

PDB ID 7l9f

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