ArticleBiophysical journal2003
Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer vestibule.
Article in Biophysical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Pooled it
- Tetrodotoxin (TTX): What do we currently know? The state of the art.Archives of toxicology · 2026Review
- The Influence of Hydroxyl Group on Nerve Excitability Blockade by Limonene and Its Hydroxylated Metabolites, Perillyl Alcohol and Carveol.Molecules (Basel, Switzerland) · 2026Article
- Toxicity Assessment of 6-Deoxytetrodotoxin by Mouse Bioassay and Its Distribution in Pufferfish.Marine drugs · 2026Article
- Voltage-Gated Sodium Channel Substitutions Underlying Tetrodotoxin Resistance in Nemerteans: Ecological and Evolutionary Implications.International journal of molecular sciences · 2025Article
- Chemical properties and biological activities of three highly purified major tetrodotoxin analogues.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Article
- The Chemistry and Biology of the Tetrodotoxin Natural Product Family.Angewandte Chemie (International ed. in English) · 2025Review
- Saxitoxin: A Comprehensive Review of Its History, Structure, Toxicology, Biosynthesis, Detection, and Preventive Implications.Marine drugs · 2025Review
- Tetrodotoxin: The State-of-the-Art Progress in Characterization, Detection, Biosynthesis, and Transport Enrichment.Marine drugs · 2024Review
- In Silico Analysis of Tetrodotoxin Binding in Voltage-Gated Sodium Ion Channels from Toxin-Resistant Animal Lineages.Marine drugs · 2022Article
- Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel.Nature biomedical engineering · 2021Article
- Article
- The gene-rich genome of the scallop Pecten maximus.GigaScience · 2020Article
- Article
- Predicting Structural Details of the Sodium Channel Pore Basing on Animal Toxin Studies.Frontiers in pharmacology · 2018Review
- Scallop genome reveals molecular adaptations to semi-sessile life and neurotoxins.Nature communications · 2017Article
- Differential binding of tetrodotoxin and its derivatives to voltage-sensitive sodium channel subtypes (NaBritish journal of pharmacology · 2017Article
- Guanidinium Toxins and Their Interactions with Voltage-Gated Sodium Ion Channels.Marine drugs · 2017Review
- Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods.EFSA journal. European Food Safety Authority · 2017Article
- Evolutionary history of a complex adaptation: tetrodotoxin resistance in salamanders.Evolution; international journal of organic evolution · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The highly selective sodium channel blocker, tetrodotoxin (TTX) has been instrumental in characterization of voltage-gated sodium channels. TTX occludes the ion-permeation pathway at the outer vestibule of the channel. In addition to a critical guanidinium group, TTX possesses six hydroxyl groups, which appear to be important for toxin block. The nature of their interactions with the outer vestibule remains debatable, however. The C-11 hydroxyl (C-11 OH) has been proposed to interact with the channel through a hydrogen bond to a carboxyl group, possibly from domain IV. On the other hand, previous experiments suggest that TTX interacts most strongly with pore loops of domains I and II. Energetic localization of the C-11 OH was undertaken by thermodynamic mutant cycle analysis assessing the dependence of the effects of mutations of the adult rat skeletal muscle Na(+) channel (rNa(v)1.4) and the presence of C-11 OH on toxin IC(50). Xenopus oocytes were injected with the mutant or native Na(+) channel mRNA, and currents were measured by two-electrode voltage clamp. Toxin blocking efficacy was determined by recording the reduction in current upon toxin exposure. Mutant cycle analysis revealed that the maximum interaction of the C-11 OH was with domain IV residue D1532 (DeltaDeltaG: 1.0 kcal/mol). Furthermore, C-11 OH had significantly less interaction with several domain I, II, and III residues. The pattern of interactions suggested that C-11 was closest to domain IV, probably involved in a hydrogen bond with the domain IV carboxyl group. Incorporating this data, a new molecular model of TTX binding is proposed.
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