Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom
| العنوان: | Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom |
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| المؤلفون: | Rym Benkhalifa, Hager Tabka, Saïd Bendahhou, Sonia Maatoug, Jean-Marie Guigonis, Sylvie Diochot, Zied Landoulsi, Amani Cheikh, Oussema Khamessi |
| المساهمون: | Biomolécules, Venins et Applications Théranostiques [Tunis], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Université de Carthage - University of Carthage, Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de PhysioMédecine Moléculaire (LP2M), This research was funded by the Tunisian Ministry of Higher Education and Scientific Research: LR11IPT08, and AFM #19928 (to SB)., UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA) |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 22 International Journal of Molecular Sciences, Vol 22, Iss 12290, p 12290 (2021) International Journal of Molecular Sciences, 2021, 22 (22), pp.12290. ⟨10.3390/ijms222212290⟩ International Journal of Molecular Sciences, MDPI, 2021, 22 (22), pp.12290. ⟨10.3390/ijms222212290⟩ |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | QH301-705.5, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, In silico, Androctonus australis, Lysine, MESH: Shaw Potassium Channels, Venom, Peptide, Kv3.1 channel, Catalysis, Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, MESH: Scorpion Venoms, 0302 clinical medicine, MESH: Xenopus laevis, open channel blocker, MESH: Potassium Channel Blockers, MESH: Molecular Docking Simulation, MESH: Animals, Biology (General), Physical and Theoretical Chemistry, Lipid bilayer, QD1-999, Molecular Biology, Spectroscopy, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, MESH: Humans, Natural product, biology, Organic Chemistry, alpha-KTx, General Medicine, biology.organism_classification, MESH: Scorpions, Computer Science Applications, Chemistry, Androctonus australis hector venom, Biochemistry, chemistry, Docking (molecular), [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030217 neurology & neurosurgery |
| الوصف: | International audience; 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 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1422-0067 1661-6596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d2bcdf793a39b014236fa9e969861beTest https://doi.org/10.3390/ijms222212290Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1d2bcdf793a39b014236fa9e969861be |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 16616596 |
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