6tx1

<table><tr><td colspan='2'>[[6tx1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Nemve Nemve]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TX1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TX1 FirstGlance]. <br>

</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">v1g201271 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=45351 NEMVE])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tx1 OCA], [http://pdbe.org/6tx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tx1 RCSB], [http://www.ebi.ac.uk/pdbsum/6tx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tx1 ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

The anti-cancer drug target poly(ADP-ribose) polymerase 1 (PARP1) and its close homologue, PARP2, are early responders to DNA damage in human cells(1,2). Upon binding to genomic lesions, these enzymes utilise NAD(+) to modify a plethora of proteins with mono- and poly(ADP-ribose) signals that are important for subsequent chromatin decompaction and repair factor recruitment(3,4). These post-translational modification events are predominantly serine-linked and require HPF1, an accessory factor that is specific for the DNA damage response and switches the amino-acid specificity of PARP1/2 from aspartate/glutamate to serine residues(5-10). Here, we report a co-structure of HPF1 bound to the catalytic domain of PARP2 that, in combination with NMR and biochemical data, reveals a composite active site formed by residues from both PARP1/2 and HPF1. We further show that the assembly of this new catalytic centre is essential for DNA damage-induced protein ADP-ribosylation in human cells. In response to DNA damage and NAD(+) binding site occupancy, the HPF1-PARP1/2 interaction is enhanced via allosteric networks operating within PARP1/2, providing an additional level of regulation in DNA repair induction. As HPF1 forms a joint active site with PARP1/2, our data implicate HPF1 as an important determinant of the response to clinical PARP inhibitors.

 

HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation.,Suskiewicz MJ, Zobel F, Ogden TEH, Fontana P, Ariza A, Yang JC, Zhu K, Bracken L, Hawthorne WJ, Ahel D, Neuhaus D, Ahel I Nature. 2020 Feb 6. pii: 10.1038/s41586-020-2013-6. doi:, 10.1038/s41586-020-2013-6. PMID:32028527<ref>PMID:32028527</ref>

 

[[Category: Nemve]]

[[Category: Ahel, I]]

[[Category: Suskiewicz, M J]]

[[Category: Serine adp-ribosylation]]