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4l6s

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Revision as of 03:53, 5 August 2016

PARP complexed with benzo[1,4]oxazin-3-one inhibitor

Structural highlights

4l6s is a 2 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:	ADPRT, PARP 1, PARP1, PPOL (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

Structure based drug design of a series of novel 1,4-benzoxazin-3-one derived PARP-1 inhibitors are described. The synthesis, enzymatic & cellular activities and pharmacodynamic effects are described. Optimized analogs demonstrated inhibition of poly-ADP-ribosylation in SW620 tumor bearing nude mice through 24h following a single dose.

Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors.,Gangloff AR, Brown J, de Jong R, Dougan DR, Grimshaw CE, Hixon M, Jennings A, Kamran R, Kiryanov A, O'Connell S, Taylor E, Vu P Bioorg Med Chem Lett. 2013 Aug 15;23(16):4501-5. doi: 10.1016/j.bmcl.2013.06.055., Epub 2013 Jun 24. PMID:23850199^[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
↑ Gangloff AR, Brown J, de Jong R, Dougan DR, Grimshaw CE, Hixon M, Jennings A, Kamran R, Kiryanov A, O'Connell S, Taylor E, Vu P. Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors. Bioorg Med Chem Lett. 2013 Aug 15;23(16):4501-5. doi: 10.1016/j.bmcl.2013.06.055., Epub 2013 Jun 24. PMID:23850199 doi:10.1016/j.bmcl.2013.06.055

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/4l6s"

@@ Line 1: / Line 1: @@
 ==PARP complexed with benzo[1,4]oxazin-3-one inhibitor==
 <StructureSection load='4l6s' size='340' side='right' caption='[[4l6s]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADPRT, PARP 1, PARP1, PPOL ([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=4l6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l6s RCSB], [http://www.ebi.ac.uk/pdbsum/4l6s 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=4l6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l6s OCA], [http://pdbe.org/4l6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4l6s RCSB], [http://www.ebi.ac.uk/pdbsum/4l6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4l6s 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 4l6s" style="background-color:#fffaf0;"></div>
 ==See Also==

4l6s

From Proteopedia

Revision as of 03:53, 5 August 2016

PARP complexed with benzo[1,4]oxazin-3-one inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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