{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:51:38Z","timestamp":1785534698372,"version":"3.56.0"},"reference-count":72,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004409","name":"Ministry of Higher Education and Scientific Research","doi-asserted-by":"publisher","award":["LR11IPT08"],"award-info":[{"award-number":["LR11IPT08"]}],"id":[{"id":"10.13039\/501100004409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004409","name":"Ministry of Higher Education and Scientific Research","doi-asserted-by":"publisher","award":["AFM #19928"],"award-info":[{"award-number":["AFM #19928"]}],"id":[{"id":"10.13039\/501100004409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms222212290","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"12290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6689-4938","authenticated-orcid":false,"given":"Sonia","family":"Maatoug","sequence":"first","affiliation":[{"name":"Laboratoire Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur BP74, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9000-5184","authenticated-orcid":false,"given":"Amani","family":"Cheikh","sequence":"additional","affiliation":[{"name":"Laboratoire Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur BP74, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-5705","authenticated-orcid":false,"given":"Oussema","family":"Khamessi","sequence":"additional","affiliation":[{"name":"Laboratoire des Biomol\u00e9cules Th\u00e9rapeutiques, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, 13 Place Pasteur BP74, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7938-3486","authenticated-orcid":false,"given":"Hager","family":"Tabka","sequence":"additional","affiliation":[{"name":"Laboratoire Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur BP74, Tunis 1002, Tunisia"},{"name":"Facult\u00e9 des Sciences de Bizerte, Universit\u00e9 de Carthage, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zied","family":"Landoulsi","sequence":"additional","affiliation":[{"name":"Laboratoire Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur BP74, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Guigonis","sequence":"additional","affiliation":[{"name":"Laboratory Transporter in Imaging and Radiotherapy in Oncology (TIRO), Direction de la Recherche Fondamentale (DRF), Institut des Sciences du Vivant Fr\u00e9deric Joliot, Commissariat \u00e0 l\u2032Energie Atomique et aux \u00c9nergies Alternatives (CEA), Universit\u00e9 C\u00f4te d\u2019Azur, F-06107 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Diochot","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 C\u00f4te d\u2019Azur, 660 Route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Bendahhou","sequence":"additional","affiliation":[{"name":"UMR7370 CNRS, LP2M, Universit\u00e9 C\u00f4te d\u2019Azur, Labex ICST, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-481X","authenticated-orcid":false,"given":"Rym","family":"Benkhalifa","sequence":"additional","affiliation":[{"name":"Laboratoire Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, 13 Place Pasteur BP74, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8111","DOI":"10.1523\/JNEUROSCI.18-20-08111.1998","article-title":"Functional and Molecular Differences between Voltage-Gated K+ Channels of Fast-Spiking Interneurons and Pyramidal Neurons of Rat Hippocampus","volume":"18","author":"Martina","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1523\/JNEUROSCI.17-09-03136.1997","article-title":"Differential Expression of K 4-AP Currents and Kv3.1 Potassium Channel Transcripts in Cortical Neurons That Develop Distinct Firing Phenotypes","volume":"17","author":"Massengill","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.neuroscience.2005.11.047","article-title":"Differential Expression of Kv3.1b and Kv3.2 Potassium Channel Subunits in Interneurons of the Basolateral Amygdala","volume":"138","author":"McDonald","year":"2006","journal-title":"Neuroscience"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1152\/jn.1992.68.3.756","article-title":"Expression of the MRNAs for the Kv3.1 Potassium Channel Gene in the Adult and Developing Rat Brain","volume":"68","author":"Perney","year":"1992","journal-title":"J. Neurophysiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0166-2236(00)01892-0","article-title":"Kv3 Channels: Voltage-Gated K+ Channels Designed for High-Frequency Repetitive Firing","volume":"24","author":"Rudy","year":"2001","journal-title":"Trends Neurosci"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1523\/JNEUROSCI.14-03-00949.1994","article-title":"Differential Expression of Shaw-Related K+ Channels in the Rat Central Nervous System","volume":"14","author":"Weiser","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.1523\/JNEUROSCI.21-17-06657.2001","article-title":"Alcohol Hypersensitivity, Increased Locomotion, and Spontaneous Myoclonus in Mice Lacking the Potassium Channels Kv3.1 and Kv3.3","volume":"21","author":"Espinosa","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1046\/j.1601-183x.2003.00054.x","article-title":"Increased Motor Drive and Sleep Loss in Mice Lacking Kv3-Type Potassium Channels","volume":"3","author":"Espinosa","year":"2004","journal-title":"Genes Brain Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1471-4159.2006.03967.x","article-title":"Selective Blockage of Kv1.3 and Kv3.1 Channels Increases Neural Progenitor Cell Proliferation","volume":"99","author":"Liebau","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1113\/jphysiol.2012.249151","article-title":"Kv3.1 Channels Stimulate Adult Neural Precursor Cell Proliferation and Neuronal Differentiation: Kv3.1 Channels in Adult Neural Precursor Cells","volume":"591","author":"Yasuda","year":"2013","journal-title":"J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tabka, H., Cheikh, A., Maatoug, S., Ayeb, M.E., Bendahhou, S., and Benkhalifa, R. (2020). First Evidence of Kv3.1b Potassium Channel Subtype Expression during Neuronal Serotonergic 1C11 Cell Line Development. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197175"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7677","DOI":"10.1523\/JNEUROSCI.23-20-07677.2003","article-title":"Motor Dysfunction and Altered Synaptic Transmission at the Parallel Fiber-Purkinje Cell Synapse in Mice Lacking Potassium Channels Kv3.1 and Kv3.3","volume":"23","author":"Matsukawa","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/neu.20112","article-title":"Aminoglycosides Block the Kv3.1 Potassium Channel and Reduce the Ability of Inferior Colliculus Neurons to Fire at High Frequencies","volume":"62","author":"Liu","year":"2005","journal-title":"J. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1254\/jphs.FP0070759","article-title":"Open Channel Block of Kv3.1 Currents by Fluoxetine","volume":"106","author":"Sung","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1152\/jn.00174.2016","article-title":"Physiological Modulators of Kv3.1 Channels Adjust Firing Patterns of Auditory Brain Stem Neurons","volume":"116","author":"Brown","year":"2016","journal-title":"J. Neurophysiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.toxicon.2013.07.012","article-title":"Scorpion Venom Components That Affect Ion-Channels Function","volume":"76","author":"Gurrola","year":"2013","journal-title":"Toxicon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.1046\/j.1432-1327.2000.01632.x","article-title":"Purification, Characterization and Molecular Modelling of Two Toxin-like Proteins from the Androctonus australis hector Venom: Natural Anatoxins","volume":"267","author":"Mansuelle","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00249-018-1323-1","article-title":"Differential effect of Androctonus australis hector venom components on macrophage KV channels: Electrophysiological characterization","volume":"48","author":"Khemili","year":"2019","journal-title":"Eur. Biophys. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbagen.2005.01.008","article-title":"Expression of the Standard Scorpion Alpha-Toxin AaH II and AaH II Mutants Leading to the Identification of Some Key Bioactive Elements","volume":"1723","author":"Legros","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.toxicon.2006.09.023","article-title":"Voltage-Gated Sodium Channel Modulation by Scorpion \u03b1-Toxins","volume":"49","author":"Bosmans","year":"2007","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1085\/jgp.201411268","article-title":"A Surface Plasmon Resonance Approach to Monitor Toxin Interactions with an Isolated Voltage-Gated Sodium Channel Paddle Motif","volume":"145","author":"Ferracci","year":"2015","journal-title":"J. Gen. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.bbrc.2019.10.115","article-title":"AaHIV a Sodium Channel Scorpion Toxin Inhibits the Proliferation of DU145 Prostate Cancer Cells","volume":"521","author":"BenAissa","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaav8573","DOI":"10.1126\/science.aav8573","article-title":"Structural Basis of \u03b1-Scorpion Toxin Action on Nav Channels","volume":"363","author":"Clairfeuille","year":"2019","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s12272-013-0176-5","article-title":"Inhibition of Human Kv3.1 Current Expressed in Xenopus Oocytes by the Toxic Venom Fraction of Androctonus australis hector","volume":"37","author":"Cheikh","year":"2014","journal-title":"Arch. Pharm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/14789450.2020.1705158","article-title":"Scorpion Venomics: A 2019 Overview","volume":"17","author":"Ortiz","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.toxicon.2004.03.022","article-title":"Current Views on Scorpion Toxins Specific for K+-Channels","volume":"43","author":"Possani","year":"2004","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0014-5793(98)01710-4","article-title":"Aah VI, a Novel, N-Glycosylated Anti-Insect Toxin from Androctonus australis hector Scorpion Venom: Isolation, Characterisation, and Glycan Structure Determination","volume":"443","author":"Hassani","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1021\/bi00458a021","article-title":"Neurotoxins Active on Insects: Amino Acid Sequences, Chemical Modifications, and Secondary Structure Estimation by Circular Dichroism of Toxins from the Scorpion Androctonus australis hector","volume":"29","author":"Loret","year":"1990","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1021\/bi00221a016","article-title":"Two-Dimensional Proton Nuclear Magnetic Resonance Study of AaH IT, an Anti-Insect Toxin from the Scorpion Androctonus australis hector. Sequential Resonance Assignments and Folding of the Polypeptide Chain","volume":"30","author":"Darbon","year":"1991","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/BF00257883","article-title":"Effects of Toxin II from the Scorpion Androctonus australis hector on Sodium Current in Neuroblastoma Cells and Their Modulation by Oleic Acid","volume":"16","author":"Jourdon","year":"1989","journal-title":"Eur. Biophys. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/BF00370889","article-title":"Changes in Na Channel Properties of Frog and Rat Skeletal Muscles Induced by the AaH II Toxin from the Scorpion Androctonus australis","volume":"415","author":"Duval","year":"1989","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1042\/bj20030688","article-title":"Characterization of Amm VIII from Androctonus Mauretanicus Mauretanicus: A New Scorpion Toxin That Discriminates between Neuronal and Skeletal Sodium Channels","volume":"375","author":"Alami","year":"2003","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.pain.2013.03.037","article-title":"The Scorpion Toxin Amm VIII Induces Pain Hypersensitivity through Gain-of-Function of TTX-Sensitive Na+ Channels","volume":"154","author":"Abbas","year":"2013","journal-title":"Pain"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/BF02192800","article-title":"Toxin III of the Scorpion Androctonus australis hector: Proton Nuclear Magnetic Resonance Assignments and Secondary Structure","volume":"2","author":"Mikou","year":"1992","journal-title":"J. Biomol. NMR"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1432-1033.1989.tb14735.x","article-title":"Structure\/Activity Relationships of Scorpion Alpha-Toxins. Multiple Residues Contribute to the Interaction with Receptors","volume":"181","author":"Kharrat","year":"1989","journal-title":"Eur. J. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1111\/j.1432-1033.1997.01118.x","article-title":"1H-NMR-Derived Secondary Structure and Overall Fold of a Natural Anatoxin from the Scorpion Androctonus australis hector","volume":"247","author":"Blanc","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0014-5793(98)00780-7","article-title":"Evidence for a New Class of Scorpion Toxins Active against K+ Channels","volume":"431","author":"Legros","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1124\/mol.113.088971","article-title":"Subtype-Selective Activation of Kv7 Channels by AaTXK \u03b2 (2\u201364), a Novel Toxin Variant from the Androctonus Australis Scorpion Venom","volume":"84","author":"Landoulsi","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1006\/bbrc.1997.7929","article-title":"A Novel Toxin from the Scorpion Androctonus australis Blocks Shaker K+ Channels Expressed in Xenopus Oocytes","volume":"242","author":"Pisciotta","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.toxicon.2014.09.005","article-title":"AaTX1, from Androctonus australis scorpion venom: Purification, synthesis and characterization in dopaminergic neurons","volume":"92","author":"Dufour","year":"2014","journal-title":"Toxicon"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S1570-9639(02)00557-5","article-title":"Functional Consequences of Deleting the Two C-Terminal Residues of the Scorpion Toxin BmTX3","volume":"1646","author":"Vacher","year":"2003","journal-title":"Biochim. Biophys. Acta (BBA) Proteins Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.bcp.2008.07.008","article-title":"A Common \u201cHot Spot\u201d Confers HERG Blockade Activity to \u03b1-Scorpion Toxins Affecting K+ Channels","volume":"76","author":"Corzo","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4196\/kjpp.2018.22.1.71","article-title":"Antidepressant Drug Paroxetine Blocks the Open Pore of Kv3.1 Potassium Channel","volume":"22","author":"Lee","year":"2018","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12272-009-1314-y","article-title":"Effect of Psoralen on the Cloned Kv3.1 Currents","volume":"32","author":"Sung","year":"2009","journal-title":"Arch. Pharm. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6744","DOI":"10.1074\/jbc.273.12.6744","article-title":"Sea Anemone Peptides with a Specific Blocking Activity against the Fast Inactivating Potassium Channel Kv3.4","volume":"273","author":"Diochot","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.1523\/JNEUROSCI.2119-05.2005","article-title":"Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS: Significance for CNS and Biophysical Studies","volume":"25","author":"Yeung","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1085\/jgp.201210890","article-title":"The Ladder-Shaped Polyether Toxin Gambierol Anchors the Gating Machinery of Kv3.1 Channels in the Resting State","volume":"141","author":"Kopljar","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0005-2736(00)00259-5","article-title":"Fast K+ Currents from Cerebellum Granular Cells Are Completely Blocked by a Peptide Puri\u00a2ed from Androctonus australis Garzoni Scorpion Venom","volume":"1468","author":"Pisciotta","year":"2000","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0014-5793(01)02620-5","article-title":"A New Class of Scorpion Toxin Binding Sites Related to an A-Type K+ Channel: Pharmacological Characterization and Localization in Rat Brain","volume":"501","author":"Vacher","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1046\/j.1432-1033.2002.03294.x","article-title":"Expanding the Scorpion Toxin \u03b1-KTX 15 Family with AmmTX3 from Androctonus Mauretanicus: Expanding the Scorpion Toxin \u03b1-KTX 15 Family","volume":"269","author":"Vacher","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/j.1460-9568.2006.05020.x","article-title":"Kv4 Channels Sensitive to BmTX3 in Rat Nervous System: Autoradiographic Analysis of Their Distribution during Brain Ontogenesis","volume":"24","author":"Vacher","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1113\/jphysiol.2012.248831","article-title":"Dipeptidyl-Peptidase-like-Proteins Confer High Sensitivity to the Scorpion Toxin AmmTX3 to Kv4-Mediated A-Type K+ Channels: DPP Proteins Confer Toxin Sensitivity to Kv4 Channels","volume":"591","author":"Maffie","year":"2013","journal-title":"J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/FBP.0000000000000107","article-title":"Kv4 Channel Blockade Reduces Motor and Neuropsychiatric Symptoms in Rodent Models of Parkinson\u2019s Disease","volume":"26","author":"Regaya","year":"2015","journal-title":"Behav. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1126\/science.2476850","article-title":"Mutant Potassium Channels with Altered Binding of Charybdotoxin, a Pore-Blocking Peptide Inhibitor","volume":"245","author":"MacKinnon","year":"1989","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.1021\/bi00144a011","article-title":"Mechanism of Iberiotoxin Block of the Large-Conductance Calcium-Activated Potassium Channel from Bovine Aortic Smooth Muscle","volume":"31","author":"Giangiacomo","year":"1992","journal-title":"Biochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"31013","DOI":"10.1074\/jbc.271.49.31013","article-title":"The Signature Sequence of Voltage-Gated Potassium Channels Projects into the External Vestibule","volume":"271","author":"Aiyar","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1432-1033.1993.tb18231.x","article-title":"Synthesis of Charybdotoxin and of Two N-Terminal Truncated Analogues. Structural and Functional Characterisation","volume":"217","author":"Vita","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1042\/BJ20041407","article-title":"A New Type of Scorpion Na+-Channel-Toxin-like Polypeptide Active on K+ Channels","volume":"388","author":"Guijarro","year":"2005","journal-title":"Biochem. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fnmol.2017.00344","article-title":"Suppression of Inflammatory Demyelinaton and Axon Degeneration through Inhibiting Kv3 Channels","volume":"10","author":"Jukkola","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Song, M., Park, S., Park, J., Byun, J., Jin, H., Seo, S., Ryu, P., and Lee, S. (2018). Kv3.1 and Kv3.4, Are Involved in Cancer Cell Migration and Invasion. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041061"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1152\/jn.1998.79.2.1081","article-title":"Differential Expression of Kv4 K+ Channel Subunits Mediating Subthreshold Transient K+ (A-Type) Currents in Rat Brain","volume":"79","author":"Rudy","year":"1998","journal-title":"J. Neurophysiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1152\/jn.1996.75.5.2174","article-title":"Cloning of a Novel Component of A-Type K+ Channels Operating at Subthreshold Potentials with Unique Expression in Heart and Brain","volume":"75","author":"Serodio","year":"1996","journal-title":"J. Neurophysiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0163-7258(02)00201-2","article-title":"K+ Channels as Therapeutic Drug Targets","volume":"94","author":"Wickenden","year":"2002","journal-title":"Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S0168-9525(00)02024-2","article-title":"EMBOSS: The European Molecular Biology Open Software Suite","volume":"16","author":"Rice","year":"2000","journal-title":"Trends Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative Protein Modelling by Satisfaction of Spatial Restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bmc.2018.12.009","article-title":"Synthesis by Native Chemical Ligation and Characterization of the Scorpion Toxin AmmTx3","volume":"27","author":"Zoukimian","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical Potential for Assessment and Prediction of Protein Structures","volume":"15","author":"Shen","year":"2006","journal-title":"Protein Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0022-2836(63)80023-6","article-title":"Stereochemistry of Polypeptide Chain Configurations","volume":"7","author":"Ramachandran","year":"1963","journal-title":"J. Mol. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/prot.340170404","article-title":"Recognition of Errors in Three-Dimensional Structures of Proteins","volume":"17","author":"Sippl","year":"1993","journal-title":"Proteins"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/356083a0","article-title":"Assessment of protein models with three-dimensional profiles","volume":"356","author":"Luthy","year":"1992","journal-title":"Nature"},{"key":"ref_71","first-page":"103608","article-title":"Potassium Channels Blockers from the Venom of Androctonus Mauretanicus Mauretanicus","volume":"2012","author":"Bougis","year":"2012","journal-title":"J. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro Web Server for Protein\u2013Protein Docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:29:56Z","timestamp":1760167796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":72,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212290"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212290","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,13]]}}}