title: Molecular approaches for structural characterization of a new potassium channel blocker from Tityus stigmurus venom: cDNA cloning, homology modeling, dynamic simulations and docking.
abstract: Potassium channels are involved in the maintenance of resting membrane potential, control of cardiac and neuronal excitability, neurotransmitters release, muscle contractility and hormone secretion. The Tityus stigmurus scorpion is widely distributed in Northeastern Brazil and known to cause severe human envenomations, inducing pain, hypoesthesia, edema, erythema, paresthesia, headaches and vomiting. Most potassium channel blocking peptides that have been purified from scorpion venoms contain 30-40 amino acids with three or four disulfide bridges. These peptides belong to α-KTx subfamily. On the other hand, the β-KTx subfamily is poorly characterized, though it is very representative in some scorpion venoms. A transcriptomic approach of T.stigmurus scorpions developed by our group revealed the repertoire of possible molecules present in the venom, including many toxins of the β-KTx subfamily. One of the ESTs found, named TSTI0003C has a cDNA sequence of 538 bp codifying a mature protein with 47 amino acid residues, corresponding to 5299 Da. This β-KTx peptide is a new member of the BmTXKβ-related toxins, and was here named TstKMK. The three-dimensional structure of this potassium channel toxin of the T. stigmurus scorpion was obtained by computational modeling and refined by molecular dynamic simulations. Furthermore, we have made docking simulations using a Shaker kV-1.2 potassium channel from rats as receptor model and proposed which amino acid residues and interactions could be involved in its blockade.
authors.affiliation: Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Diego Dantas
authors.initials: DD
authors.lastname: Almeida
authors.forename: Taffarel Melo
authors.initials: TM
authors.lastname: Torres
authors.forename: Euzébio Guimarães
authors.initials: EG
authors.lastname: Barbosa
authors.forename: João Paulo Matos Santos
authors.initials: JP
authors.lastname: Lima
authors.forename: Matheus
authors.initials: M
authors.lastname: de Freitas Fernandes-Pedrosa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D026902:Potassium Channel Blockers / Q000737:chemistry*; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics; D012605:Scorpions / Q000737:chemistry* / Q000235:genetics
chemical_list: D018076:DNA, Complementary; C581017:KMK peptide, Tityus stigmurus; D010455:Peptides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms