6Z8C
Crystal Structure of the Voltage-Gated Sodium Channel NavMs (F208L) in complex with N-desmethyltamoxifen (3.2 A resolution)
Summary for 6Z8C
| Entry DOI | 10.2210/pdb6z8c/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 | 33275.30 |
| Authors | Sula, A.,Hollingworth, D.,Wallace, B.A. (deposition date: 2020-06-02, release date: 2021-02-03, Last modification date: 2024-01-24) |
| Primary citation | Sula, A.,Hollingworth, D.,Ng, L.C.T.,Larmore, M.,DeCaen, P.G.,Wallace, B.A. A tamoxifen receptor within a voltage-gated sodium channel. Mol.Cell, 81:1160-, 2021 Cited by PubMed Abstract: Voltage-gated sodium channels are targets for many analgesic and antiepileptic drugs whose therapeutic mechanisms and binding sites have been well characterized. We describe the identification of a previously unidentified receptor site within the NavMs voltage-gated sodium channel. Tamoxifen, an estrogen receptor modulator, and its primary and secondary metabolic products bind at the intracellular exit of the channel, which is a site that is distinct from other previously characterized sodium channel drug sites. These compounds inhibit NavMs and human sodium channels with similar potencies and prevent sodium conductance by delaying channel recovery from the inactivated state. This study therefore not only describes the structure and pharmacology of a site that could be leveraged for the development of new drugs for the treatment of sodium channelopathies but may also have important implications for off-target health effects of this widely used therapeutic drug. PubMed: 33503406DOI: 10.1016/j.molcel.2020.12.048 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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