6tx2

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<StructureSection load='6tx2' size='340' side='right'caption='[[6tx2]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
<StructureSection load='6tx2' size='340' side='right'caption='[[6tx2]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6tx2]] is a 1 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=6TX2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TX2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6tx2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TX2 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.09&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HPF1, C4orf27 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tx2 OCA], [http://pdbe.org/6tx2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tx2 RCSB], [http://www.ebi.ac.uk/pdbsum/6tx2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tx2 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tx2 OCA], [https://pdbe.org/6tx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tx2 RCSB], [https://www.ebi.ac.uk/pdbsum/6tx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tx2 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/HPF1_HUMAN HPF1_HUMAN]] Acts as a cofactor for serine ADP-ribosylation by conferring serine specificity on PARP1 and PARP2: interacts with PARP1 and PARP2 and is able to change amino acid specificity toward serine (PubMed:28190768, PubMed:29480802). Promotes histone serine ADP-ribosylation in response to DNA damage, limiting DNA damage-induced PARP1 hyper-automodification, and ensuring genome stability (PubMed:27067600, PubMed:28190768). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1 (PubMed:30257210).<ref>PMID:27067600</ref> <ref>PMID:28190768</ref> <ref>PMID:29480802</ref> <ref>PMID:30257210</ref>
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[https://www.uniprot.org/uniprot/HPF1_HUMAN HPF1_HUMAN] Acts as a cofactor for serine ADP-ribosylation by conferring serine specificity on PARP1 and PARP2: interacts with PARP1 and PARP2 and is able to change amino acid specificity toward serine (PubMed:28190768, PubMed:29480802). Promotes histone serine ADP-ribosylation in response to DNA damage, limiting DNA damage-induced PARP1 hyper-automodification, and ensuring genome stability (PubMed:27067600, PubMed:28190768). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1 (PubMed:30257210).<ref>PMID:27067600</ref> <ref>PMID:28190768</ref> <ref>PMID:29480802</ref> <ref>PMID:30257210</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6tx2" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Ahel, I]]
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[[Category: Ahel I]]
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[[Category: Suskiewicz, M J]]
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[[Category: Suskiewicz MJ]]
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[[Category: Adp-ribosylation]]
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[[Category: C4orf27]]
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[[Category: Parp1]]
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[[Category: Parp2]]
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[[Category: Protein binding]]
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[[Category: Serine adp-ribosylation]]
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Current revision

Human HPF1

PDB ID 6tx2

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