6v3w
From Proteopedia
(Difference between revisions)
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<StructureSection load='6v3w' size='340' side='right'caption='[[6v3w]], [[Resolution|resolution]] 2.04Å' scene=''> | <StructureSection load='6v3w' size='340' side='right'caption='[[6v3w]], [[Resolution|resolution]] 2.04Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V3W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V3W 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]] 2.04Å</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]] 2.04Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=QO4:5-{[(2S)-1-(3-oxo-3-{4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}propoxy)propan-2-yl]amino}-4-(trifluoromethyl)pyridazin-3(2H)-one'>QO4</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=QO4:5-{[(2S)-1-(3-oxo-3-{4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}propoxy)propan-2-yl]amino}-4-(trifluoromethyl)pyridazin-3(2H)-one'>QO4</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=6v3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v3w OCA], [https://pdbe.org/6v3w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v3w RCSB], [https://www.ebi.ac.uk/pdbsum/6v3w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v3w 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=6v3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v3w OCA], [https://pdbe.org/6v3w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v3w RCSB], [https://www.ebi.ac.uk/pdbsum/6v3w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v3w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [https://www.uniprot.org/uniprot/PAR12_HUMAN PAR12_HUMAN] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function. Here, we identify PARP7 as a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 restores type I interferon (IFN) signaling responses to nucleic acids in tumor models. Restored signaling can directly inhibit cell proliferation and activate the immune system, both of which contribute to tumor regression. Oral dosing of the PARP7 small-molecule inhibitor, RBN-2397, results in complete tumor regression in a lung cancer xenograft and induces tumor-specific adaptive immune memory in an immunocompetent mouse cancer model, dependent on inducing type I IFN signaling in tumor cells. PARP7 is a therapeutic target whose inhibition induces both cancer cell-autonomous and immune stimulatory effects via enhanced IFN signaling. These data support the targeting of a monoPARP in cancer and introduce a potent and selective PARP7 inhibitor to enter clinical development. | ||
| - | |||
| - | PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity.,Gozgit JM, Vasbinder MM, Abo RP, Kunii K, Kuplast-Barr KG, Gui B, Lu AZ, Molina JR, Minissale E, Swinger KK, Wigle TJ, Blackwell DJ, Majer CR, Ren Y, Niepel M, Varsamis ZA, Nayak SP, Bamberg E, Mo JR, Church WD, Mady ASA, Song J, Utley L, Rao PE, Mitchison TJ, Kuntz KW, Richon VM, Keilhack H Cancer Cell. 2021 Jul 22. pii: S1535-6108(21)00340-8. doi:, 10.1016/j.ccell.2021.06.018. PMID:34375612<ref>PMID:34375612</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 6v3w" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] | *[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gozgit JM]] | [[Category: Gozgit JM]] | ||
Current revision
Human Poly(ADP-Ribose) Polymerase 12, Catalytic fragment with four point mutations in complex with RBN-2397
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