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| | <StructureSection load='6wkn' size='340' side='right'caption='[[6wkn]], [[Resolution|resolution]] 3.46Å' scene=''> | | <StructureSection load='6wkn' size='340' side='right'caption='[[6wkn]], [[Resolution|resolution]] 3.46Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wkn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WKN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wkn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WKN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LQ4:piperlongumine'>LQ4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.46Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv2, Sac2b, Vrl1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LQ4:piperlongumine'>LQ4</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=6wkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wkn OCA], [https://pdbe.org/6wkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wkn RCSB], [https://www.ebi.ac.uk/pdbsum/6wkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wkn 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=6wkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wkn OCA], [https://pdbe.org/6wkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wkn RCSB], [https://www.ebi.ac.uk/pdbsum/6wkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wkn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TRPV2_RAT TRPV2_RAT]] Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by growth factors, like IGF1, PDGF and morphogenetic neuropeptide/head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH (By similarity).<ref>PMID:10201375</ref> <ref>PMID:15249591</ref>
| + | [https://www.uniprot.org/uniprot/TRPV2_RAT TRPV2_RAT] Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by growth factors, like IGF1, PDGF and morphogenetic neuropeptide/head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH (By similarity).<ref>PMID:10201375</ref> <ref>PMID:15249591</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. The structure of the PL-bound full-length rat TRPV2 channel was determined by cryo-EM. PL binds to a transient allosteric pocket responsible for a new mode of anticancer activity against glioblastoma (GBM) in which hTRPV2 is overexpressed. Calcium imaging experiments revealed the importance of Arg539 and Thr522 residues on the antagonistic effect of PL and calcium influx modulation of the TRPV2 channel. Downregulation of hTRPV2 reduces sensitivity to PL and decreases ROS production. Analysis of GBM patient samples associates hTRPV2 overexpression with tumor grade, disease progression, and poor prognosis. Extensive tumor abrogation and long term survival was achieved in two murine models of orthotopic GBM by formulating PL in an implantable scaffold/hydrogel for sustained local therapy. Furthermore, in primary tumor samples derived from GBM patients, we observed a selective reduction of malignant cells in response to PL ex vivo. Our results establish a broadly applicable strategy, leveraging data-motivated research hypotheses for the discovery of novel means tackling cancer.
| + | |
| | | | |
| - | Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression.,Conde J, Pumroy RA, Baker C, Rodrigues T, Guerreiro A, Sousa BB, Marques MC, de Almeida BP, Lee S, Leites EP, Picard D, Samanta A, Vaz SH, Sieglitz F, Langini M, Remke M, Roque R, Weiss T, Weller M, Liu Y, Han S, Corzana F, Morais VA, Faria CC, Carvalho T, Filippakopoulos P, Snijder B, Barbosa-Morais NL, Moiseenkova-Bell VY, Bernardes GJL ACS Cent Sci. 2021 May 26;7(5):868-881. doi: 10.1021/acscentsci.1c00070. Epub, 2021 Apr 14. PMID:34079902<ref>PMID:34079902</ref>
| + | ==See Also== |
| - | | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6wkn" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Moiseenkova-Bell, V Y]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Pumroy, R P]] | + | [[Category: Moiseenkova-Bell VY]] |
| - | [[Category: Ion channel]] | + | [[Category: Pumroy RP]] |
| - | [[Category: Piperlongumine]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Trp channel]]
| + | |
| - | [[Category: Trpv2]]
| + | |
