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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 ; Tietze, Alesia A. ; Tietze, Daniel (2019)
In Silico Analysis of the Subtype Selective Blockage of KCNA Ion Channels through the µ-Conotoxins PIIIA, SIIIA, and GIIIA.
In: Marine Drugs, 2019, (3)
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: In Silico Analysis of the Subtype Selective Blockage of KCNA Ion Channels through the µ-Conotoxins PIIIA, SIIIA, and GIIIA
Language: English
Date: 2019
Place of Publication: Darmstadt
Year of primary publication: 2019
Publisher: MDPI
Journal or Publication Title: Marine Drugs
Issue Number: 3
Series Volume: 17
Corresponding Links:
Origin: Secondary publication via sponsored Golden Open Access
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.

Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-86642
Classification DDC: 500 Science and mathematics > 540 Chemistry
Divisions: 07 Department of Chemistry > Eduard Zintl-Institut > Physical Chemistry
Date Deposited: 29 Apr 2019 10:25
Last Modified: 13 Dec 2022 10:02
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/8664
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