ArticleBiophysical journal2002
Energetic localization of saxitoxin in its channel binding site.
Article in Biophysical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- A designer saxitoxin-engineered sodium channel pair as a general tool for subtype-selective inhibition.Cell chemical biology · 2026Article
- A chemogenetic ligand-receptor pair for voltage-gated sodium channel subtype-selective inhibition.bioRxiv : the preprint server for biology · 2025Article
- Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.Nature communications · 2025Article
- Guanidinium Toxins and Their Interactions with Voltage-Gated Sodium Ion Channels.Marine drugs · 2017Review
- Mutant cycle analysis with modified saxitoxins reveals specific interactions critical to attaining high-affinity inhibition of hNaV1.7.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Enzyme-luminescence method: Tool for real-time monitoring of natural neurotoxins in vitro and l-glutamate release from primary cortical neurons.Biotechnology reports (Amsterdam, Netherlands) · 2016Article
- Chronic toxicity study of neosaxitoxin in rats.Marine drugs · 2014Article
- Use-dependent block of the voltage-gated Na(+) channel by tetrodotoxin and saxitoxin: effect of pore mutations that change ionic selectivity.The Journal of general physiology · 2012Article
- Cooccupancy of the outer vestibule of voltage-gated sodium channels by micro-conotoxin KIIIA and saxitoxin or tetrodotoxin.Journal of neurophysiology · 2010Article
- The tetrodotoxin binding site is within the outer vestibule of the sodium channel.Marine drugs · 2010Review
- De novo synthesis of modified saxitoxins for sodium ion channel study.Journal of the American Chemical Society · 2009Article
- A stereoselective synthesis of (+)-gonyautoxin 3.Journal of the American Chemical Society · 2008Article
- Differential interactions of Na+ channel toxins with T-type Ca2+ channels.The Journal of general physiology · 2008Article
- The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: a potent sodium-channel blocker.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Tonic and phasic guanidinium toxin-block of skeletal muscle Na channels expressed in Mammalian cells.Biophysical journal · 2003Article
- Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer vestibule.Biophysical journal · 2003Article
- Docking of mu-conotoxin GIIIA in the sodium channel outer vestibule.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Saxitoxin (STX) selectively blocks the voltage-gated sodium channel at the outer vestibule lined by P-loops of the four domains. Neosaxitoxin has an additional -OH group at the N1 position of the 1,2,3 guanidinium (N1-OH) that interacts with domains I and IV of the Na(+) channel. Determination of a second toxin interaction with the channel would fix the location of STX. Gonyautoxin 2,3 and Gonyautoxin 1,4 are C-11 sulfated derivatives of saxitoxin and neosaxitoxin, respectively. We used these variants to constrain the STX docking orientation by energetically localizing the C-11 sulfate in the outer vestibule. Interactions between the C-11 sulfate and each of the four domains of the channel were determined by a systematic approach to mutant cycle analysis in which all known carboxyl groups important for site 1 toxin binding were neutralized, allowing energetic triangulation of the toxin sulfate and overcoming some limitations of mutant cycles. Toxin IC(50)s were measured by two-electrode voltage clamp from Xenopus oocytes injected with the channel mRNA. Three unique types of analysis based on the coupling results localized the C-11 sulfate between domains III and IV. Combined with our previous report, the data establish the orientation of STX in the outer vestibule and confirm the clockwise arrangement of the channel domains.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.