title: A subfamily of acidic alpha-K(+) toxins.
abstract: Three homologous acidic peptides have been isolated from the venom of three different Parabuthus scorpion species, P. transvaalicus, P. villosus, and P. granulatus. Analysis of the primary sequences reveals that they structurally belong to subfamily 11 of short chain alpha-K(+)-blocking peptides (Tytgat, J., Chandy, K. G., Garcia, M. L., Gutman, G. A., Martin-Eauclaire, M. F., van der Walt, J. J., and Possani, L. D. (1999) Trends Pharmacol. Sci. 20, 444-447). These toxins are 36-37 amino acids in length and have six aligned cysteine residues, but they differ substantially from the other alpha-K(+) toxins because of the absence of the critical Lys(27) and their total overall negative charge. Parabutoxin 1 (PBTx1), which has been expressed by recombinant methods, has been submitted to functional characterization. Despite the lack of the Lys(27), this toxin blocks several Kv1-type channels heterologously expressed in Xenopus oocytes but with low affinities (micromolar range). Because a relationship between the biological activity and the acidic residue substitutions may exist, we set out to elucidate the relative impact of the acidic character of the toxin and the lack of the critical Lys(27) on the weak activity of PBTx1 toward Kv1 channels. To achieve this, a specific mutant named rPBTx1 T24F/V26K was made recombinantly and fully characterized on Kv1-type channels heterologously expressed in Xenopus oocytes. Analysis of rPBTx1 T24F/V26K displaying an affinity toward Kv1.2 and Kv1.3 channels in the nanomolar range shows the importance of the functional dyad above the acidic character of this toxin.
authors.affiliation: Laboratory of Toxicology, University of Leuven, E Van Evenstraat 4, 3000 Leuven, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Huys
authors.forename: Timoteo
authors.initials: T
authors.lastname: Olamendi-Portugal
authors.forename: Blanca Ines
authors.initials: BI
authors.lastname: Garcia-Gómez
authors.forename: Isabel
authors.initials: I
authors.lastname: Vandenberghe
authors.forename: Jozef
authors.initials: J
authors.lastname: Van Beeumen
authors.forename: Karin
authors.initials: K
authors.lastname: Dyason
authors.forename: Elke
authors.initials: E
authors.lastname: Clynen
authors.forename: Shunyi
authors.initials: S
authors.lastname: Zhu
authors.forename: Jurg
authors.initials: J
authors.lastname: van der Walt
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D015640:Ion Channel Gating / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions; D016415:Sequence Alignment
chemical_list: D009498:Neurotoxins; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms