View source for 3c49


==Human poly(ADP-ribose) polymerase 3, catalytic fragment in complex with an inhibitor KU0058948==
<StructureSection load='3c49' size='340' side='right'caption='[[3c49]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3c49]] 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=3C49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C49 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KU8:4-[3-(1,4-DIAZEPAN-1-YLCARBONYL)-4-FLUOROBENZYL]PHTHALAZIN-1(2H)-ONE'>KU8</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=3c49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c49 OCA], [https://pdbe.org/3c49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c49 RCSB], [https://www.ebi.ac.uk/pdbsum/3c49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c49 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PARP3_HUMAN PARP3_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. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing.<ref>PMID:16924674</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c4/3c49_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3c49 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures highlight key features for potent inhibitor binding and suggest routes for creating isoenzyme-specific PARP inhibitors.

Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.,Lehtio L, Jemth AS, Collins R, Loseva O, Johansson A, Markova N, Hammarstrom M, Flores A, Holmberg-Schiavone L, Weigelt J, Helleday T, Schuler H, Karlberg T J Med Chem. 2009 May 14;52(9):3108-11. PMID:19354255<ref>PMID:19354255</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3c49" style="background-color:#fffaf0;"></div>

==See Also==
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Berglund H]]
[[Category: Bountra C]]
[[Category: Busam R]]
[[Category: Collins R]]
[[Category: Dahlgren LG]]
[[Category: Edwards AM]]
[[Category: Flodin S]]
[[Category: Flores A]]
[[Category: Graslund S]]
[[Category: Hammarstrom M]]
[[Category: Helleday T]]
[[Category: Herman MD]]
[[Category: Johansson A]]
[[Category: Johansson I]]
[[Category: Kallas A]]
[[Category: Karlberg T]]
[[Category: Kotenyova T]]
[[Category: Lehtio L]]
[[Category: Moche M]]
[[Category: Nilsson ME]]
[[Category: Nordlund P]]
[[Category: Nyman T]]
[[Category: Persson C]]
[[Category: Sagemark J]]
[[Category: Svensson L]]
[[Category: Thorsell AG]]
[[Category: Tresaugues L]]
[[Category: Van den Berg S]]
[[Category: Weigelt J]]
[[Category: Welin M]]