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| | ==The X-ray crystal structure of poly(ADP-ribose) glycohydrolase bound to the inhibitor ADP-HPD from Thermomonospora curvata== | | ==The X-ray crystal structure of poly(ADP-ribose) glycohydrolase bound to the inhibitor ADP-HPD from Thermomonospora curvata== |
| - | <StructureSection load='3sii' size='340' side='right' caption='[[3sii]], [[Resolution|resolution]] 1.48Å' scene=''> | + | <StructureSection load='3sii' size='340' side='right'caption='[[3sii]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3sii]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Thermomonospora_curvata Thermomonospora curvata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SII OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SII FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3sii]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermomonospora_curvata_DSM_43183 Thermomonospora curvata DSM 43183]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SII FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A1R:5-O-[(S)-{[(S)-{[(2R,3R,4S)-3,4-DIHYDROXYPYRROLIDIN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]ADENOSINE'>A1R</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.48Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sig|3sig]], [[3sih|3sih]], [[3sij|3sij]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1R:5-O-[(S)-{[(S)-{[(2R,3R,4S)-3,4-DIHYDROXYPYRROLIDIN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]ADENOSINE'>A1R</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tcur_1721 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2020 Thermomonospora curvata])</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=3sii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sii OCA], [https://pdbe.org/3sii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sii RCSB], [https://www.ebi.ac.uk/pdbsum/3sii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sii ProSAT]</span></td></tr> |
| - | <tr><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>
| + | </table> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sii OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sii RCSB], [http://www.ebi.ac.uk/pdbsum/3sii PDBsum]</span></td></tr> | + | == Function == |
| - | <table> | + | [https://www.uniprot.org/uniprot/D1AC29_THECD D1AC29_THECD] |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed == | + | |
| - | Post-translational modification of proteins by poly(ADP-ribosyl)ation regulates many cellular pathways that are critical for genome stability, including DNA repair, chromatin structure, mitosis and apoptosis. Poly(ADP-ribose) (PAR) is composed of repeating ADP-ribose units linked via a unique glycosidic ribose-ribose bond, and is synthesized from NAD by PAR polymerases. PAR glycohydrolase (PARG) is the only protein capable of specific hydrolysis of the ribose-ribose bonds present in PAR chains; its deficiency leads to cell death. Here we show that filamentous fungi and a number of bacteria possess a divergent form of PARG that has all the main characteristics of the human PARG enzyme. We present the first PARG crystal structure (derived from the bacterium Thermomonospora curvata), which reveals that the PARG catalytic domain is a distant member of the ubiquitous ADP-ribose-binding macrodomain family. High-resolution structures of T. curvata PARG in complexes with ADP-ribose and the PARG inhibitor ADP-HPD, complemented by biochemical studies, allow us to propose a model for PAR binding and catalysis by PARG. The insights into the PARG structure and catalytic mechanism should greatly improve our understanding of how PARG activity controls reversible protein poly(ADP-ribosyl)ation and potentially of how the defects in this regulation are linked to human disease.
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| - | The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase.,Slade D, Dunstan MS, Barkauskaite E, Weston R, Lafite P, Dixon N, Ahel M, Leys D, Ahel I Nature. 2011 Sep 4. doi: 10.1038/nature10404. PMID:21892188<ref>PMID:21892188</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[Poly(ADP-ribose) glycohydrolase 3D structures|Poly(ADP-ribose) glycohydrolase 3D structures]] |
| - | == References == | + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Thermomonospora curvata]] | + | [[Category: Large Structures]] |
| - | [[Category: Dunstan, M S.]] | + | [[Category: Thermomonospora curvata DSM 43183]] |
| - | [[Category: Leys, D.]] | + | [[Category: Dunstan MS]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | [[Category: Leys D]] |
