8hks
From Proteopedia
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<table><tr><td colspan='2'>[[8hks]] 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=8HKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HKS FirstGlance]. <br> | <table><tr><td colspan='2'>[[8hks]] 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=8HKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HKS 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]] 2.8Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=8hks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hks OCA], [https://pdbe.org/8hks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hks RCSB], [https://www.ebi.ac.uk/pdbsum/8hks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hks ProSAT]</span></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=8hks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hks OCA], [https://pdbe.org/8hks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hks RCSB], [https://www.ebi.ac.uk/pdbsum/8hks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hks ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_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. | [https://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The PARP-1/2 inhibitors have been approved for the treatment of cancers by modulating the enzymatic activity and/or the trapping ability for damaged DNA of PARP-1 and/or PARP-2, and the selective PARP-1 inhibitors are now attracting considerable attention with an aim to search for drug candidates with an improved safety. Exploring the structural basis of the selectivity and trapping capability of known PARP-1/2 inhibitors would be beneficial for the discovery of the improved inhibitors. Herein, a mutated PARP-2 catalytic domain, designated as catPARP-2SE, was engineered. It could be expressed in an elevated level and had capability to crystalize at 25 degrees C, which greatly facilitated obtaining PARP-2 crystals. Consequently, the complex structures of Fluzoparib, Pamiparib, Rucaparib, and Niraparib within PARP-2 were achieved. Taking advantage of these complexed structures, the detailed and quantitative analyses of protein-ligand and intra-protein interactions (alphaB-alphaF, alphaJ-alphaB, alphaJ-alphaF, ASL-alphaD and ASL-alphaF interfaces) were conducted with quantum chemistry methods (GFN2-xTB and IGMH). It suggested that the residues adjacent to Asp766 in the HD and ASL domains and the alphaJ-alphaF and ASL-alphaD interfaces were closely related to the selectivity and trapping mechanism. These results would provide some insights for the design and development of novel PARP-1/2 inhibitors with improved pharmacodynamic properties. | ||
| + | |||
| + | Engaging an engineered PARP-2 catalytic domain mutant to solve the complex structures harboring approved drugs for structure analyses.,Wang X, Zhou J, Xu B Bioorg Chem. 2025 Jun 15;160:108471. doi: 10.1016/j.bioorg.2025.108471. Epub 2025 , Apr 12. PMID:40228437<ref>PMID:40228437</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8hks" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to Pamiparib(BGB-290)
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Categories: Homo sapiens | Large Structures | Wang XY | Xu BL | Zhou J
