A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus.
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 4000.3Da, 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 alpha-KTx 2.13.
Corzo
Gerardo
G
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, UNAM, Apartado Postal 510-3, Cuernavaca Morelos 62250, Mexico.
Papp
Ferenc
F
Varga
Zoltan
Z
Barraza
Omar
O
Espino-Solis
Pavel G
PG
Rodríguez de la Vega
Ricardo C
RC
Gaspar
Rezso
R
Panyi
Gyorgy
G
Possani
Lourival D
LD
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D051663:Kv1.2 Potassium Channel / Q000037:antagonists & inhibitors* / Q000502:physiology; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012605:Scorpions
D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms