4gv7

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{{STRUCTURE_4gv7| PDB=4gv7 | SCENE= }}
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==Human ARTD1 (PARP1) - Catalytic domain in complex with inhibitor ME0328==
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===Human ARTD1 (PARP1) - Catalytic domain in complex with inhibitor ME0328===
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<StructureSection load='4gv7' size='340' side='right' caption='[[4gv7]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23742272}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4gv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GV7 FirstGlance]. <br>
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==Function==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MEW:2-METHYLQUINAZOLIN-4(3H)-ONE'>MEW</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4gv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gv7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gv7 RCSB], [http://www.ebi.ac.uk/pdbsum/4gv7 PDBsum]</span></td></tr>
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</table>
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== Function ==
[[http://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_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. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
[[http://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_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. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:23742272</ref>
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[[4gv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GV7 OCA].
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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>
==See Also==
==See Also==
*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]]
*[[Poly (ADP-ribose) polymerase|Poly (ADP-ribose) polymerase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023742272</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Andersson, C D.]]
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[[Category: Andersson, C D]]
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[[Category: Ekblad, T.]]
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[[Category: Ekblad, T]]
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[[Category: Elofsson, M.]]
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[[Category: Elofsson, M]]
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[[Category: Karlberg, T.]]
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[[Category: Karlberg, T]]
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[[Category: Lindgren, A E.G.]]
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[[Category: Lindgren, A E.G]]
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[[Category: Linusson, A.]]
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[[Category: Linusson, A]]
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[[Category: Schuler, H.]]
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[[Category: Schuler, H]]
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[[Category: Spjut, S.]]
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[[Category: Spjut, S]]
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[[Category: Thorsell, A G.]]
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[[Category: Thorsell, A G]]
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[[Category: Weigelt, J.]]
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[[Category: Weigelt, J]]
[[Category: Adp-ribose]]
[[Category: Adp-ribose]]
[[Category: Adp-ribose transferase]]
[[Category: Adp-ribose transferase]]

Revision as of 19:38, 24 December 2014

Human ARTD1 (PARP1) - Catalytic domain in complex with inhibitor ME0328

4gv7, resolution 2.89Å

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