A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus |
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Authors: | Corzo Gerardo Papp Ferenc Varga Zoltan Barraza Omar Espino-Solis Pavel G Rodríguez de la Vega Ricardo C Gaspar Rezso Panyi Gyorgy Possani Lourival D |
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Institution: | a Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, UNAM. Apartado Postal 510-3, Cuernavaca Morelos 62250, Mexico b Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen 4012, Hungary c Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen 4012, Hungary |
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Abstract: | A novel potassium channel blocker peptide was purified from the venom of the scorpion Centruroides suffusus suffusus by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4000.3 Da, tightly folded by three disulfide bridges. This peptide, named Css20, was shown to block preferentially the currents of the voltage-dependent K+-channels Kv1.2 and Kv1.3. It did not affect several other ion channels tested at 10 nM concentration. Concentration-response curves of Css20 yielded an IC50 of 1.3 and 7.2 nM for Kv1.2- and Kv1.3-channels, respectively. Interestingly, despite the similar affinities for the two channels the association and dissociation rates of the toxin were much slower for Kv1.2, implying that different interactions may be involved in binding to the two channel types; an implication further supported by in silico docking analyses. Based on the primary structure of Css20, the systematic nomenclature proposed for this toxin is α-KTx 2.13. |
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Keywords: | Cos cells a monkey African green kidney derived cell line EGTA ethylene glycol tetraacetic acid GFP green fluorescent protein HEK cells human embryo kidney cell line hERG human ERG K+-channel HEPES 4-(2-hydroethyl)-1-piperazineethanesulfonic acid hNav human voltage-gated Na+-channel IKCa1 calcium-dependent inward-rectifier K+-channel rKv2 1 rat voltage-gated K+-channel subtype 2 1 HPLC high-performance liquid chromatography MTX maurotoxin TFA trifluoroacetic acid R M S D root mean square deviation |
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