6tx1: Difference between revisions
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==HPF1 from Nematostella vectensis== | |||
<StructureSection load='6tx1' size='340' side='right'caption='[[6tx1]], [[Resolution|resolution]] 2.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6tx1]] is a 2 chain structure. 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TX1 FirstGlance]. <br> | |||
</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=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> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6tx1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Ahel, I]] | |||
[[Category: Suskiewicz, M J]] | |||
[[Category: Adaptor]] | |||
[[Category: Adp-ribosylation]] | |||
[[Category: Parp1]] | |||
[[Category: Parp2]] | |||
[[Category: Protein binding]] | |||
[[Category: Serine adp-ribosylation]] | |||
