8sp8: Difference between revisions

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-'''Unreleased structure'''
-The entry 8sp8 is ON HOLD
+==Human TRP channel TRPV6 in cNW30 nanodiscs inhibited by tetrahydrocannabivarin (THCV)==
+<StructureSection load='8sp8' size='340' side='right'caption='[[8sp8]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8sp8]] 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=8SP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SP8 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.79&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=I8E:Tetrahydrocannabivarin'>I8E</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8sp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sp8 OCA], [https://pdbe.org/8sp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sp8 RCSB], [https://www.ebi.ac.uk/pdbsum/8sp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sp8 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TRPV6_HUMAN TRPV6_HUMAN] Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:11097838, PubMed:11278579, PubMed:11248124 PubMed:15184369, PubMed:23612980). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:15184369). Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating.[UniProtKB:Q91WD2]<ref>PMID:11097838</ref> <ref>PMID:11248124</ref> <ref>PMID:11278579</ref> <ref>PMID:15184369</ref> <ref>PMID:23612980</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The calcium-selective oncochannel TRPV6 is an important driver of cell proliferation in human cancers. Despite increasing interest of pharmacological research in developing synthetic inhibitors of TRPV6, natural compounds acting at this channel have been largely neglected. On the other hand, pharmacokinetics of natural small-molecule antagonists optimized by nature throughout evolution endows these compounds with a medicinal potential to serve as potent and safe next-generation anti-cancer drugs. Here we report the structure of human TRPV6 in complex with tetrahydrocannabivarin (THCV), a natural cannabinoid inhibitor extracted from Cannabis sativa. We use cryo-electron microscopy combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to identify THCV binding sites in the portals that connect the membrane environment surrounding the protein to the central cavity of the channel pore and to characterize the allosteric mechanism of TRPV6 inhibition. We also propose the molecular pathway taken by THCV to reach its binding site. Our study provides a foundation for the development of new TRPV6-targeting drugs.
-Authors:
+Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin.,Neuberger A, Trofimov YA, Yelshanskaya MV, Khau J, Nadezhdin KD, Khosrof LS, Krylov NA, Efremov RG, Sobolevsky AI Nat Commun. 2023 Aug 2;14(1):4630. doi: 10.1038/s41467-023-40362-2. PMID:37532722<ref>PMID:37532722</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8sp8" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Nadezhdin KD]]
+[[Category: Neuberger A]]
+[[Category: Sobolevsky AI]]
+[[Category: Yelshanskaya MV]]