title: Novel K(+)-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch.
abstract: Two novel toxins were purified from the venom of the Mexican scorpion Centruroides limpidus limpidus, using an immunoassay based on antibodies raised against noxiustoxin (NTX), a known K(+)-channel-blocker-peptide. The primary structure of C. l. limpidus toxin 1 was obtained by Edman degradation and was shown to be composed of 38 amino acid residues, containing six half-cystines. The first 36 residues of C. l. limpidus toxin 2 were also determined. Both toxins are capable of displacing the binding of radio-labelled NTX to rat brain synaptosomes with high affinity (about 100 pM). These toxins are capable of inhibiting transient K(+)-currents (resembling IA-type currents), in cultured rat cerebellar granule cells. About 50% of the peak currents are reduced by application of a 1.5 microM solution of toxins 1 and 2 The K+ current reduction is partially reversible, under washing but not voltage-dependent. Comparison of the primary structure of C. l. limpidus toxin 1 with other known toxins shows 74% identity with margatoxin, 64% with NTX, 51% with kaliotoxin, 39% with iberiotoxin, 37% with charybdotoxin and Lq2, and 29% with leirutoxin 1. The only invariant amino acids in all these toxins are the six cysteines, a glycine in position 26 and two lysines at positions 28 and 33, respectively. The relevance of these differences in terms of possible structure-function relationships is discussed.
authors.affiliation: National Institute of Mental Health, Molecular Neurogenetics Unit, Bethesda, MD 20892.
authors.forename: B M
authors.initials: BM
authors.lastname: Martin
authors.forename: A N
authors.initials: AN
authors.lastname: Ramirez
authors.forename: G B
authors.initials: GB
authors.lastname: Gurrola
authors.forename: M
authors.initials: M
authors.lastname: Nobile
authors.forename: G
authors.initials: G
authors.lastname: Prestipino
authors.forename: L D
authors.initials: LD
authors.lastname: Possani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D003429:Cross Reactions; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000276:immunology / Q000302:isolation & purification*
chemical_list: D000911:Antibodies, Monoclonal; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D014118:Toxins, Biological; C052567:noxiustoxin