ArticleChannels (Austin, Tex.)2016
Mutant bacterial sodium channels as models for local anesthetic block of eukaryotic proteins.
Article in Channels (Austin, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Drugs exhibit diverse binding modes and access routes in the Nav1.5 cardiac sodium channel pore.The Journal of general physiology · 2025Article
- Noncanonical Ion Channel Behaviour in Pain.International journal of molecular sciences · 2019Review
- Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Physical basis of specificity and delayed binding of a subtype selective sodium channel inhibitor.Scientific reports · 2018Article
- Phenytoin: a step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology.Journal of neurology · 2017Article
- Germs against pain: Humanized bacterial sodium channels.Channels (Austin, Tex.) · 2016Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Voltage gated sodium channels are the target of a range of local anesthetic, anti-epileptic and anti-arrhythmic compounds. But, gaining a molecular level understanding of their mode of action is difficult as we only have atomic resolution structures of bacterial sodium channels not their eukaryotic counterparts. In this study we used molecular dynamics simulations to demonstrate that the binding sites of both the local anesthetic benzocaine and the anti-epileptic phenytoin to the bacterial sodium channel NavAb can be altered significantly by the introduction of point mutations. Free energy techniques were applied to show that increased aromaticity in the pore of the channel, used to emulate the aromatic residues observed in eukaryotic Nav1.2, led to changes in the location of binding and dissociation constants of each drug relative to wild type NavAb. Further, binding locations and dissociation constants obtained for both benzocaine (660 μM) and phenytoin (1 μM) in the mutant channels were within the range expected from experimental values obtained from drug binding to eukaryotic sodium channels, indicating that these mutant NavAb may be a better model for drug binding to eukaryotic channels than the wild type.
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