6YZ0
Full length Open-form Sodium Channel NavMs F208L in complex with Cannabidiol (CBD)
Summary for 6YZ0
| Entry DOI | 10.2210/pdb6yz0/pdb |
| Descriptor | Ion transport protein, SODIUM ION, HEGA-10, ... (6 entities in total) |
| Functional Keywords | voltage gated sodium channel, membrane protein., metal transport |
| Biological source | Magnetococcus marinus MC-1 |
| Total number of polymer chains | 1 |
| Total formula weight | 32497.31 |
| Authors | Sula, A.,Sait, L.G.,Hollingworth, D.,Wallace, B.A. (deposition date: 2020-05-06, release date: 2020-11-11, Last modification date: 2024-01-24) |
| Primary citation | Sait, L.G.,Sula, A.,Ghovanloo, M.R.,Hollingworth, D.,Ruben, P.C.,Wallace, B.A. Cannabidiol interactions with voltage-gated sodium channels. Elife, 9:-, 2020 Cited by PubMed Abstract: 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. PubMed: 33089780DOI: 10.7554/eLife.58593 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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