title: Characterization of Kbot21 Reveals Novel Side Chain Interactions of Scorpion Toxins Inhibiting Voltage-Gated Potassium Channels.
abstract: Scorpion toxins are important pharmacological tools for probing the physiological roles of ion channels which are involved in many physiological processes and as such have significant therapeutic potential. The discovery of new scorpion toxins with different specificities and affinities is needed to further characterize the physiology of ion channels. In this regard, a new short polypeptide called Kbot21 has been purified to homogeneity from the venom of Buthus occitanus tunetanus scorpion. Kbot21 is structurally related to BmBKTx1 from the venom of the Asian scorpion Buthus martensii Karsch. These two toxins differ by only two residues at position 13 (R /V) and 24 (D/N).Despite their very similar sequences, Kbot21 and BmBKTx1 differ in their electrophysiological activities. Kbot21 targets KV channel subtypes whereas BmBKTx1 is active on both big conductance (BK) and small conductance (SK) Ca2+-activated K+ channel subtypes, but has no effects on Kv channel subtypes. The docking model of Kbot21 with the Kv1.2 channel shows that the D24 and R13 side-chain of Kbot21 are critical for its interaction with KV channels.
authors.affiliation: Laboratoire des Venins et Molécules Thérapeutiques, Institut Pasteur de Tunis,13 Place Pasteur, BP-74, 1002, Tunis, Tunisie.
authors.forename: Rym
authors.initials: R
authors.lastname: ElFessi-Magouri
authors.affiliation: Laboratory of Toxicology & Pharmacology, University of Leuven (K.U. Leuven), Campus Gasthuisberg O&N2, Herestraat 49, P.O. Box 922, B-3000, Leuven, Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.affiliation: Laboratoire des Venins et Molécules Thérapeutiques, Institut Pasteur de Tunis,13 Place Pasteur, BP-74, 1002, Tunis, Tunisie.
authors.forename: Houcemeddine
authors.initials: H
authors.lastname: Othman
authors.affiliation: Laboratoire des Venins et Molécules Thérapeutiques, Institut Pasteur de Tunis,13 Place Pasteur, BP-74, 1002, Tunis, Tunisie.
authors.forename: Najet
authors.initials: N
authors.lastname: Srairi-Abid
authors.affiliation: Laboratoire des Venins et Molécules Thérapeutiques, Institut Pasteur de Tunis,13 Place Pasteur, BP-74, 1002, Tunis, Tunisie.
authors.forename: Mohamed
authors.initials: M
authors.lastname: ElAyeb
authors.affiliation: Laboratory of Toxicology & Pharmacology, University of Leuven (K.U. Leuven), Campus Gasthuisberg O&N2, Herestraat 49, P.O. Box 922, B-3000, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.affiliation: Laboratoire des Venins et Molécules Thérapeutiques, Institut Pasteur de Tunis,13 Place Pasteur, BP-74, 1002, Tunis, Tunisie.
authors.forename: Riadh
authors.initials: R
authors.lastname: Kharrat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity*; D016415:Sequence Alignment; D014981:Xenopus
chemical_list: D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms