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In Silico Analysis of the Subtype Selective Blockage of KCNA Ion Channels through the µ-Conotoxins PIIIA, SIIIA, and GIIIA

Kaufmann, Desirée and Tietze, Alesia A. and Tietze, Daniel (2019):
In Silico Analysis of the Subtype Selective Blockage of KCNA Ion Channels through the µ-Conotoxins PIIIA, SIIIA, and GIIIA.
17, In: Marine Drugs, (3), MDPI, p. 180, ISSN 1660-3397,
DOI: 10.3390/md17030180,
Secondary publishing via sponsored Golden Open Access, [Article]

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Item Type: Article
Origin: Secondary publishing via sponsored Golden Open Access
Title: In Silico Analysis of the Subtype Selective Blockage of KCNA Ion Channels through the µ-Conotoxins PIIIA, SIIIA, and GIIIA
Language: English
Abstract:

Understanding subtype specific ion channel pore blockage by natural peptide-based toxins is crucial for developing such compounds into promising drug candidates. Herein, docking and molecular dynamics simulations were employed in order to understand the dynamics and binding states of the µ-conotoxins, PIIIA, SIIIA, and GIIIA, at the voltage-gated potassium channels of the KV1 family, and they were correlated with their experimental activities recently reported by Leipold et al. Their different activities can only adequately be understood when dynamic information about the toxin-channel systems is available. For all of the channel-bound toxins investigated herein, a certain conformational flexibility was observed during the molecular dynamic simulations, which corresponds to their bioactivity. Our data suggest a similar binding mode of µ-PIIIA at KV1.6 and KV1.1, in which a plethora of hydrogen bonds are formed by the Arg and Lys residues within the α-helical core region of µ-PIIIA, with the central pore residues of the channel. Furthermore, the contribution of the K+ channel’s outer and inner pore loops with respect to the toxin binding. and how the subtype specificity is induced, were proposed.

Journal or Publication Title: Marine Drugs
Volume: 17
Number: 3
Publisher: MDPI
Classification DDC: 500 Naturwissenschaften und Mathematik > 540 Chemie
Divisions: 07 Department of Chemistry > Physical Chemistry
Date Deposited: 29 Apr 2019 10:25
Last Modified: 22 Jan 2020 07:40
DOI: 10.3390/md17030180
URN: urn:nbn:de:tuda-tuprints-86642
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/8664
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