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| | <StructureSection load='5dsy' size='340' side='right'caption='[[5dsy]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='5dsy' size='340' side='right'caption='[[5dsy]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dsy]] 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=5DSY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DSY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dsy]] 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=5DSY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DSY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UHB:2-[4-[(2S,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]CARBONYLPIPERAZIN-1-YL]-N-(1-OXIDANYLIDENE-2,3-DIHYDROISOINDOL-4-YL)ETHANAMIDE'>UHB</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]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP2, ADPRT2, ADPRTL2 ([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=UHB:2-[4-[(2S,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]CARBONYLPIPERAZIN-1-YL]-N-(1-OXIDANYLIDENE-2,3-DIHYDROISOINDOL-4-YL)ETHANAMIDE'>UHB</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=5dsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dsy OCA], [https://pdbe.org/5dsy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dsy RCSB], [https://www.ebi.ac.uk/pdbsum/5dsy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dsy ProSAT]</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=5dsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dsy OCA], [http://pdbe.org/5dsy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dsy RCSB], [http://www.ebi.ac.uk/pdbsum/5dsy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dsy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. | + | [https://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pascal, J M]] | + | [[Category: Pascal JM]] |
| - | [[Category: Riccio, A A]] | + | [[Category: Riccio AA]] |
| - | [[Category: Adp-ribosyl transferase]]
| + | |
| - | [[Category: Parp]]
| + | |
| - | [[Category: Parp-2]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PARP2_HUMAN Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
Publication Abstract from PubMed
Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. The mechanism for tight control of the robust catalytic potential of PARP-1 remains unclear. By monitoring PARP-1 dynamics using hydrogen/deuterium exchange-mass spectrometry (HXMS), we unexpectedly find that a specific portion of the helical subdomain (HD) of the catalytic domain rapidly unfolds when PARP-1 encounters a DNA break. Together with biochemical and crystallographic analysis of HD deletion mutants, we show that the HD is an autoinhibitory domain that blocks productive NAD(+) binding. Our molecular model explains how PARP-1 DNA damage detection leads to local unfolding of the HD that relieves autoinhibition, and has important implications for the design of PARP inhibitors.
PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.,Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD, Karch KR, McCauley M, Steffen JD, Black BE, Pascal JM Mol Cell. 2015 Dec 3;60(5):755-68. doi: 10.1016/j.molcel.2015.10.013. Epub 2015, Nov 25. PMID:26626480[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD, Karch KR, McCauley M, Steffen JD, Black BE, Pascal JM. PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain. Mol Cell. 2015 Dec 3;60(5):755-68. doi: 10.1016/j.molcel.2015.10.013. Epub 2015, Nov 25. PMID:26626480 doi:http://dx.doi.org/10.1016/j.molcel.2015.10.013
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