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| | ==Human ARTD3 (PARP3) - Catalytic domain in complex with inhibitor ME0354== | | ==Human ARTD3 (PARP3) - Catalytic domain in complex with inhibitor ME0354== |
| - | <StructureSection load='4gv2' size='340' side='right' caption='[[4gv2]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4gv2' size='340' side='right'caption='[[4gv2]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gv2]] is a 1 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=4GV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GV2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gv2]] is a 1 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=4GV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GV2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5ME:3-(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)-N-[(1R)-1-(PYRIDIN-2-YL)ETHYL]PROPANAMIDE'>5ME</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5ME:3-(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)-N-[(1R)-1-(PYRIDIN-2-YL)ETHYL]PROPANAMIDE'>5ME</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gv0|4gv0]], [[4gv4|4gv4]]</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=4gv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gv2 OCA], [https://pdbe.org/4gv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gv2 RCSB], [https://www.ebi.ac.uk/pdbsum/4gv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gv2 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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>
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| - | <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=4gv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gv2 OCA], [http://pdbe.org/4gv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gv2 RCSB], [http://www.ebi.ac.uk/pdbsum/4gv2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gv2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PARP3_HUMAN PARP3_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. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing.<ref>PMID:16924674</ref> | + | [https://www.uniprot.org/uniprot/PARP3_HUMAN PARP3_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. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing.<ref>PMID:16924674</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]] | + | *[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Andersson, C D]] | + | [[Category: Large Structures]] |
| - | [[Category: Ekblad, T]] | + | [[Category: Andersson CD]] |
| - | [[Category: Elofsson, M]] | + | [[Category: Ekblad T]] |
| - | [[Category: Karlberg, T]] | + | [[Category: Elofsson M]] |
| - | [[Category: Lindgren, A E.G]] | + | [[Category: Karlberg T]] |
| - | [[Category: Linusson, A]] | + | [[Category: Lindgren AEG]] |
| - | [[Category: Schuler, H]] | + | [[Category: Linusson A]] |
| - | [[Category: Spjut, S]] | + | [[Category: Schuler H]] |
| - | [[Category: Thorsell, A G]] | + | [[Category: Spjut S]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Thorsell AG]] |
| - | [[Category: Adp- ribosylation]]
| + | [[Category: Weigelt J]] |
| - | [[Category: Adp-ribose]]
| + | |
| - | [[Category: Adp-ribosylation]]
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| - | [[Category: Artd transferase domain]]
| + | |
| - | [[Category: Artd3]]
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| - | [[Category: Nad]]
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| - | [[Category: Parp3]]
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| - | [[Category: Transferase]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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| Structural highlights
Function
PARP3_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. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing.[1]
Publication Abstract from PubMed
Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12 members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at sub-micromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
A PARP inhibitor with selectivity toward ADP-ribosyltransferase ARTD3/PARP3.,Lindgren AE, Karlberg T, Thorsell AG, Hesse M, Spjut S, Ekblad T, Andersson CD, Pinto AF, Weigelt J, Hottiger MO, Linusson A, Elofsson M, Schuler H ACS Chem Biol. 2013 Jun 6. PMID:23742272[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rouleau M, McDonald D, Gagne P, Ouellet ME, Droit A, Hunter JM, Dutertre S, Prigent C, Hendzel MJ, Poirier GG. PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery. J Cell Biochem. 2007 Feb 1;100(2):385-401. PMID:16924674 doi:10.1002/jcb.21051
- ↑ Lindgren AE, Karlberg T, Thorsell AG, Hesse M, Spjut S, Ekblad T, Andersson CD, Pinto AF, Weigelt J, Hottiger MO, Linusson A, Elofsson M, Schuler H. A PARP inhibitor with selectivity toward ADP-ribosyltransferase ARTD3/PARP3. ACS Chem Biol. 2013 Jun 6. PMID:23742272 doi:10.1021/cb4002014
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