View source for 9dmc


==Human PARP1 ART domain bound to NAD+ analog benzamide adenine dinucleotide and ADP-ribose==
<StructureSection load='9dmc' size='340' side='right'caption='[[9dmc]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dmc]] is a 4 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=9DMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DMC 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=DQV:[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+[(2R,3S,4R,5S)-5-(3-carbamoylphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+dihydrogen+diphosphate+(non-preferred+name)'>DQV</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=9dmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dmc OCA], [https://pdbe.org/9dmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dmc RCSB], [https://www.ebi.ac.uk/pdbsum/9dmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dmc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_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. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PARP enzymes transfer ADP-ribose from NAD(+) onto proteins as a covalent modification that regulates multiple aspects of cell biology. Here, we identify an undiscovered catalytic activity for human PARP1: de novo generation of free PAR molecules that are not attached to proteins. Free PAR production arises when a molecule of NAD(+) or ADP-ribose docks in the PARP1 acceptor site and attaches to an NAD(+) molecule bound to the donor site, releasing nicotinamide and initiating ADP-ribose chains that emanate from NAD(+)/ADP-ribose rather than protein. Free PAR is also produced by human PARP2 and the PARP enzyme Tankyrase. We demonstrate that free PAR in cells is generated mostly by PARP1 de novo synthesis activity rather than by PAR-degrading enzymes PAR glycohydrolase (PARG), ARH3, and TARG1 releasing PAR from protein. The coincident production of free PAR and protein-linked modifications alters models for PAR signaling and broadens the scope of PARP enzyme signaling capacity.

PARP enzyme de novo synthesis of protein-free poly(ADP-ribose).,Langelier MF, Mirhasan M, Gilbert K, Sverzhinksy A, Furtos A, Pascal JM Mol Cell. 2024 Dec 19;84(24):4758-4773.e6. doi: 10.1016/j.molcel.2024.10.024. , Epub 2024 Nov 12. PMID:39536748<ref>PMID:39536748</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9dmc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Langelier MF]]
[[Category: Pascal JM]]