6tvh: Difference between revisions

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~~'''Unreleased structure'''~~

The ~~entry 6tvh~~ is ~~ON HOLD~~

==Selenomethionine-substituted HPF1 from Nematostella vectensis==

== Structural highlights ==

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

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.651Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>

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

</table>

== Function ==

[https://www.uniprot.org/uniprot/HPF1_NEMVE HPF1_NEMVE] Cofactor for serine ADP-ribosylation that confers serine specificity on PARP. Switches the amino acid specificity of PARP from aspartate or glutamate to serine residues. Acts by completing the active site of PARP: forms a composite active site composed of residues from HPF1 and PARP.[UniProtKB:Q9NWY4]

== 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.

~~Authors~~:

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>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Nematostella vectensis]]

[[Category: Ariza A]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6tvh is ON HOLD
+==Selenomethionine-substituted HPF1 from Nematostella vectensis==
+<StructureSection load='6tvh' size='340' side='right'caption='[[6tvh]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6tvh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nematostella_vectensis Nematostella vectensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TVH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.651&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tvh OCA], [https://pdbe.org/6tvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tvh RCSB], [https://www.ebi.ac.uk/pdbsum/6tvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tvh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HPF1_NEMVE HPF1_NEMVE] Cofactor for serine ADP-ribosylation that confers serine specificity on PARP. Switches the amino acid specificity of PARP from aspartate or glutamate to serine residues. Acts by completing the active site of PARP: forms a composite active site composed of residues from HPF1 and PARP.[UniProtKB:Q9NWY4]
+<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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6tvh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Nematostella vectensis]]
+[[Category: Ariza A]]