Structure-function study of a chlorotoxin-chimer and its activity on Kv1.3 channels.
Chlorotoxin has been isolated from the venom of the scorpion Leiurus quinquestriatus and characterized as a 4.1kDa peptide, containing a lysine at position 27 that is also present in many Kv-blocking toxins. Because chlorotoxin shows no affinity for Kv-channels, we intended to design, express and purify a chlorotoxin-chimer, containing the active binding site (beta-sheet) of a very potent Kv1-channel blocking peptide, agitoxin 2, by mutating three original residues in the chlorotoxin molecule. Several derivatives of the chimer, gradually missing one additional amino acid residue at the N-terminal side of the peptide, were produced and identified chromatographically. In contrast to chlorotoxin, these chimer derivatives are capable of blocking cloned Kv1-channels.
Huys
Isabelle
I
Laboratory of Toxicology, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, E. Van Evenstraat 4, 3000 Leuven, Belgium.
Waelkens
Etienne
E
Tytgat
Jan
J
D000595:Amino Acid Sequence; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D015951:Factor Xa / Q000378:metabolism; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D012604:Scorpion Venoms; C091539:Chlorotoxin; D015951:Factor Xa