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9etr

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Crystal structure of PARP1 catalytic domain bound to AZD9574

Structural highlights

9etr is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.822Å
Ligands:	,
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]

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