ArticlePloS one2014
Mechanism of μ-conotoxin PIIIA binding to the voltage-gated Na+ channel NaV1.4.
Article in PloS one, 2014. 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, 33 citations in OpenAlex.
- In Silico Conotoxin Studies: Progress and Prospects.Molecules (Basel, Switzerland) · 2024Review
- Review
- Functional effects of drugs and toxins interacting with NaFrontiers in pharmacology · 2024Review
- Historical Perspective of the Characterization of Conotoxins Targeting Voltage-Gated Sodium Channels.Marine drugs · 2023Review
- Brevetoxin and Conotoxin Interactions with Single-Domain Voltage-Gated Sodium Channels from a Diatom and Coccolithophore.Marine drugs · 2021Article
- Extremely Potent Block of Bacterial Voltage-Gated Sodium Channels by µ-Conotoxin PIIIA.Marine drugs · 2019Article
- Effect of Conformational Diversity on the Bioactivity of µ-Conotoxin PIIIA Disulfide Isomers.Marine drugs · 2019Article
- In Silico Analysis of the Subtype Selective Blockage of KCNA Ion Channels through the µ-Conotoxins PIIIA, SIIIA, and GIIIA.Marine drugs · 2019Article
- Snails In Silico: A Review of Computational Studies on the Conopeptides.Marine drugs · 2019Review
- µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic Potential.Marine drugs · 2017Review
- Molecular Simulations of Disulfide-Rich Venom Peptides with Ion Channels and Membranes.Molecules (Basel, Switzerland) · 2017Review
- Article
- Article
- Article
- Computational approaches for designing potent and selective analogs of peptide toxins as novel therapeutics.Future medicinal chemistry · 2014Review
- Folding similarity of the outer pore region in prokaryotic and eukaryotic sodium channels revealed by docking of conotoxins GIIIA, PIIIA, and KIIIA in a NavAb-based model of Nav1.4.The Journal of general physiology · 2014Article
- Binding modes of two scorpion toxins to the voltage-gated potassium channel kv1.3 revealed from molecular dynamics.Toxins · 2014Article
- Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.PloS one · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several subtypes of voltage-gated Na+ (NaV) channels are important targets for pain management. μ-Conotoxins isolated from venoms of cone snails are potent and specific blockers of different NaV channel isoforms. The inhibitory effect of μ-conotoxins on NaV channels has been examined extensively, but the mechanism of toxin specificity has not been understood in detail. Here the known structure of μ-conotoxin PIIIA and a model of the skeletal muscle channel NaV1.4 are used to elucidate elements that contribute to the structural basis of μ-conotoxin binding and specificity. The model of NaV1.4 is constructed based on the crystal structure of the bacterial NaV channel, NaVAb. Six different binding modes, in which the side chain of each of the basic residues carried by the toxin protrudes into the selectivity filter of NaV1.4, are examined in atomic detail using molecular dynamics simulations with explicit solvent. The dissociation constants (Kd) computed for two selected binding modes in which Lys9 or Arg14 from the toxin protrudes into the filter of the channel are within 2 fold; both values in close proximity to those determined from dose response data for the block of NaV currents. To explore the mechanism of PIIIA specificity, a double mutant of NaV1.4 mimicking NaV channels resistant to μ-conotoxins and tetrodotoxin is constructed and the binding of PIIIA to this mutant channel examined. The double mutation causes the affinity of PIIIA to reduce by two orders of magnitude.
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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 Socratic graph.