6yz0: Difference between revisions
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==Full length Open-form Sodium Channel NavMs F208L in complex with Cannabidiol (CBD)== | |||
<StructureSection load='6yz0' size='340' side='right'caption='[[6yz0]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6yz0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Magnetococcus_marinus_MC-1 Magnetococcus marinus MC-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YZ0 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=2CV:HEGA-10'>2CV</scene>, <scene name='pdbligand=CD0:2-[(1R,2R,5S)-5-methyl-2-(prop-1-en-2-yl)cyclohexyl]-5-pentylbenzene-1,3-diol'>CD0</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6yz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yz0 OCA], [https://pdbe.org/6yz0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yz0 RCSB], [https://www.ebi.ac.uk/pdbsum/6yz0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yz0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0L5S6_MAGMM A0L5S6_MAGMM] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels. | |||
Cannabidiol interactions with voltage-gated sodium channels.,Sait LG, Sula A, Ghovanloo MR, Hollingworth D, Ruben PC, Wallace BA Elife. 2020 Oct 22;9. pii: 58593. doi: 10.7554/eLife.58593. PMID:33089780<ref>PMID:33089780</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6yz0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ion channels 3D structures|Ion channels 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Magnetococcus marinus MC-1]] | |||
[[Category: Hollingworth D]] | |||
[[Category: Sait LG]] | |||
[[Category: Sula A]] | |||
[[Category: Wallace BA]] | |||
Latest revision as of 16:38, 24 January 2024
Structural highlights
FunctionPublication Abstract from PubMedVoltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels. Cannabidiol interactions with voltage-gated sodium channels.,Sait LG, Sula A, Ghovanloo MR, Hollingworth D, Ruben PC, Wallace BA Elife. 2020 Oct 22;9. pii: 58593. doi: 10.7554/eLife.58593. PMID:33089780[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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