Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom

The voltage-gated K+ channels Kv3.1 display fast activation and deactivation kinetics and are known to have a crucial contribution to the fast-spiking phenotype of certain neurons. AahG50, as a natural product extracted from Androctonus australis hector veno...

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Autores principales:	Sonia Maatoug, Amani Cheikh, Oussema Khamessi, Hager Tabka, Zied Landoulsi, Jean-Marie Guigonis, Sylvie Diochot, Saïd Bendahhou, Rym Benkhalifa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Kv3.1 channel <i>Androctonus australis hector</i> venom open channel blocker alpha-KTx Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f1589d1d72c34914a1494d435f104141
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spelling	oai:doaj.org-article:f1589d1d72c34914a1494d435f1041412021-11-25T17:55:05ZCross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom10.3390/ijms2222122901422-00671661-6596https://doaj.org/article/f1589d1d72c34914a1494d435f1041412021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12290https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The voltage-gated K<sup>+</sup> channels Kv3.1 display fast activation and deactivation kinetics and are known to have a crucial contribution to the fast-spiking phenotype of certain neurons. AahG50, as a natural product extracted from <i>Androctonus australis hector</i> venom, inhibits selectively Kv3.1 channels. In the present study, we focused on the biochemical and pharmacological characterization of the component in AahG50 scorpion venom that potently and selectively blocks the Kv3.1 channels. We used a combined optimization through advanced biochemical purification and patch-clamp screening steps to characterize the peptide in AahG50 active on Kv3.1 channels. We described the inhibitory effect of a toxin on Kv3.1 unitary current in black lipid bilayers. In silico, docking experiments are used to study the molecular details of the binding. We identified the first scorpion venom peptide inhibiting Kv3.1 current at 170 nM. This toxin is the alpha-KTx 15.1, which occludes the Kv3.1 channel pore by means of the lysine 27 lateral chain. This study highlights, for the first time, the modulation of the Kv3.1 by alpha-KTx 15.1, which could be an interesting starting compound for developing therapeutic biomolecules against Kv3.1-associated diseases.Sonia MaatougAmani CheikhOussema KhamessiHager TabkaZied LandoulsiJean-Marie GuigonisSylvie DiochotSaïd BendahhouRym BenkhalifaMDPI AGarticleKv3.1 channel<i>Androctonus australis hector</i> venomopen channel blockeralpha-KTxBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12290, p 12290 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Kv3.1 channel <i>Androctonus australis hector</i> venom open channel blocker alpha-KTx Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Kv3.1 channel <i>Androctonus australis hector</i> venom open channel blocker alpha-KTx Biology (General) QH301-705.5 Chemistry QD1-999 Sonia Maatoug Amani Cheikh Oussema Khamessi Hager Tabka Zied Landoulsi Jean-Marie Guigonis Sylvie Diochot Saïd Bendahhou Rym Benkhalifa Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom
description	The voltage-gated K<sup>+</sup> channels Kv3.1 display fast activation and deactivation kinetics and are known to have a crucial contribution to the fast-spiking phenotype of certain neurons. AahG50, as a natural product extracted from <i>Androctonus australis hector</i> venom, inhibits selectively Kv3.1 channels. In the present study, we focused on the biochemical and pharmacological characterization of the component in AahG50 scorpion venom that potently and selectively blocks the Kv3.1 channels. We used a combined optimization through advanced biochemical purification and patch-clamp screening steps to characterize the peptide in AahG50 active on Kv3.1 channels. We described the inhibitory effect of a toxin on Kv3.1 unitary current in black lipid bilayers. In silico, docking experiments are used to study the molecular details of the binding. We identified the first scorpion venom peptide inhibiting Kv3.1 current at 170 nM. This toxin is the alpha-KTx 15.1, which occludes the Kv3.1 channel pore by means of the lysine 27 lateral chain. This study highlights, for the first time, the modulation of the Kv3.1 by alpha-KTx 15.1, which could be an interesting starting compound for developing therapeutic biomolecules against Kv3.1-associated diseases.
format	article
author	Sonia Maatoug Amani Cheikh Oussema Khamessi Hager Tabka Zied Landoulsi Jean-Marie Guigonis Sylvie Diochot Saïd Bendahhou Rym Benkhalifa
author_facet	Sonia Maatoug Amani Cheikh Oussema Khamessi Hager Tabka Zied Landoulsi Jean-Marie Guigonis Sylvie Diochot Saïd Bendahhou Rym Benkhalifa
author_sort	Sonia Maatoug
title	Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom
title_short	Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom
title_full	Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom
title_fullStr	Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom
title_full_unstemmed	Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom
title_sort	cross pharmacological, biochemical and computational studies of a human kv3.1b inhibitor from <i>androctonus australis</i> venom
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f1589d1d72c34914a1494d435f104141
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Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from <i>Androctonus australis</i> Venom

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