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4gv7

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Revision as of 21:05, 4 August 2016

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

Structural highlights

4gv7 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	PARP1 (HUMAN)
Activity:	NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maruyama T, Nara K, Yoshikawa H, Suzuki N. Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells. Clin Exp Immunol. 2007 Jan;147(1):164-75. PMID:17177976 doi:10.1111/j.1365-2249.2006.03249.x
↑ Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC. Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature. 2008 Jan 3;451(7174):81-5. doi: 10.1038/nature06420. PMID:18172500 doi:10.1038/nature06420
↑ Reinemund J, Seidel K, Steckelings UM, Zaade D, Klare S, Rompe F, Katerbaum M, Schacherl J, Li Y, Menk M, Schefe JH, Goldin-Lang P, Szabo C, Olah G, Unger T, Funke-Kaiser H. Poly(ADP-ribose) polymerase-1 (PARP-1) transcriptionally regulates angiotensin AT2 receptor (AT2R) and AT2R binding protein (ATBP) genes. Biochem Pharmacol. 2009 Jun 15;77(12):1795-805. doi: 10.1016/j.bcp.2009.02.025., Epub 2009 Mar 19. PMID:19344625 doi:10.1016/j.bcp.2009.02.025
↑ Ahel D, Horejsi Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ. Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science. 2009 Sep 4;325(5945):1240-3. doi: 10.1126/science.1177321. Epub 2009 Aug, 6. PMID:19661379 doi:10.1126/science.1177321
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gv7"

@@ Line 1: / Line 1: @@
 ==Human ARTD1 (PARP1) - Catalytic domain in complex with inhibitor ME0328==
 <StructureSection load='4gv7' size='340' side='right' caption='[[4gv7]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[4gv7]] 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=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>
 </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>
-<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>
+<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 HUMAN])</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'>[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>
+<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://pdbe.org/4gv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gv7 RCSB], [http://www.ebi.ac.uk/pdbsum/4gv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gv7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4gv7" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Andersson, C D]]
 [[Category: Ekblad, T]]

4gv7

From Proteopedia

Revision as of 21:05, 4 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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