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Investigation of toxin binding to bacterial voltage-gated sodium ion channels
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
2018 (English)Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
Abstract [en]

Voltage-gated sodium ion channels are membrane proteins that initiate the action potentials in nerves, endocrine and muscle cells. A group of selected neurotoxins and conotoxins were found to have an effect on the excitation and inhibition of the bacterial voltage-gated sodium channels. This fact provides an opportunity to obtain a more detailed description of the molecular mechanism by which the sodium channel governs the communication within cells, with the aid of the studied toxins. In order to investigate this possibility, we employed a combination of computational and experimental methods. Computational techniques aimed to provide the atomistic details of interaction between toxins and the sodium channel where the data obtained were correlated with experimental studies in vitro. Interestingly, among the studied toxins, the binding modes for neurotoxin (TX1) and conotoxin (TX5) were found to be different where TX1 revealed a higher binding affinity to the sodium channel in comparison with that observed for TX5 (docking and thermodynamic work calculations). An explanation to this behavior was believed to be due to the higher number of interaction points formed between TX1 and NavAb originating from different bound conformations of that toxin at the pore of the sodium channel. Initial experimental validation of TX1 binding to the sodium channel using surface plasmon resonance technique demonstrated concentration dependent binding. Based upon the observed behavior of TX1, an SPR binding assay can be developed. Altogether, the results obtained in this work not only reflect the complexity of toxin binding to sodium channels, but the potential of using a combination of computational methods and biochemical assay for the development of new protein drugs for therapy.

Place, publisher, year, edition, pages
2018.
Keywords [en]
Voltage-gated sodium channel, conotoxin, neurotoxin, molecular dynamics, protein–protein docking, binding assay
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:lnu:diva-77203OAI: oai:DiVA.org:lnu-77203DiVA, id: diva2:1240211
Subject / course
Chemistry
Educational program
Chemistry Master Programme, 120 credits
Supervisors
Examiners
Available from: 2018-08-21 Created: 2018-08-20 Last updated: 2018-08-21Bibliographically approved

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CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf