8adj
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Poly(ADP-ribose) glycohydrolase (PARG) from Drosophila melanogaster in complex with PARG inhibitor PDD00017272== | |
| + | <StructureSection load='8adj' size='340' side='right'caption='[[8adj]], [[Resolution|resolution]] 2.51Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8adj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ADJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ADJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LQX:1-[(2,5-dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-bis(oxidanylidene)quinazoline-6-sulfonamide'>LQX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8adj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8adj OCA], [https://pdbe.org/8adj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8adj RCSB], [https://www.ebi.ac.uk/pdbsum/8adj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8adj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PARG_DROME PARG_DROME] Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. Poly(ADP-ribose) metabolism is required for maintenance of the normal function of neuronal cells.<ref>PMID:14676324</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In the mammalian DNA damage response, ADP-ribosylation signalling is of crucial importance to mark sites of DNA damage as well as recruit and regulate repairs factors. Specifically, the PARP1:HPF1 complex recognises damaged DNA and catalyses the formation of serine-linked ADP-ribosylation marks (mono-Ser-ADPr), which are extended into ADP-ribose polymers (poly-Ser-ADPr) by PARP1 alone. Poly-Ser-ADPr is reversed by PARG, while the terminal mono-Ser-ADPr is removed by ARH3. Despite its significance and apparent evolutionary conservation, little is known about ADP-ribosylation signalling in non-mammalian Animalia. The presence of HPF1, but absence of ARH3, in some insect genomes, including Drosophila species, raises questions regarding the existence and reversal of serine-ADP-ribosylation in these species. Here we show by quantitative proteomics that Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster and is dependent on the dParp1:dHpf1 complex. Moreover, our structural and biochemical investigations uncover the mechanism of mono-Ser-ADPr removal by Drosophila Parg. Collectively, our data reveal PARP:HPF1-mediated Ser-ADPr as a defining feature of the DDR in Animalia. The striking conservation within this kingdom suggests that organisms that carry only a core set of ADP-ribosyl metabolising enzymes, such as Drosophila, are valuable model organisms to study the physiological role of Ser-ADPr signalling. | ||
| - | + | Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling.,Fontana P, Buch-Larsen SC, Suyari O, Smith R, Suskiewicz MJ, Schutzenhofer K, Ariza A, Rack JGM, Nielsen ML, Ahel I Nat Commun. 2023 Jun 2;14(1):3200. doi: 10.1038/s41467-023-38793-y. PMID:37268618<ref>PMID:37268618</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8adj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Drosophila melanogaster]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ariza A]] | ||
| + | [[Category: Fontana P]] | ||
Revision as of 08:14, 14 June 2023
Poly(ADP-ribose) glycohydrolase (PARG) from Drosophila melanogaster in complex with PARG inhibitor PDD00017272
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