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6sxc

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Crystal structure of the Voltage-Gated Sodium Channel NavMs (F208L) in complex with 4-hydroxytamoxifen (2.5 Angstrom resolution)

Structural highlights

6sxc is a 1 chain structure with sequence from Magnetococcus marinus MC-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0L5S6_MAGMM

Publication Abstract from PubMed

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.

A tamoxifen receptor within a voltage-gated sodium channel.,Sula A, Hollingworth D, Ng LCT, Larmore M, DeCaen PG, Wallace BA Mol Cell. 2021 Mar 18;81(6):1160-1169.e5. doi: 10.1016/j.molcel.2020.12.048. Epub , 2021 Jan 26. PMID:33503406^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sula A, Hollingworth D, Ng LCT, Larmore M, DeCaen PG, Wallace BA. A tamoxifen receptor within a voltage-gated sodium channel. Mol Cell. 2021 Mar 18;81(6):1160-1169.e5. PMID:33503406 doi:10.1016/j.molcel.2020.12.048