Novel K(+)-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch.
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.
Martin
B M
BM
National Institute of Mental Health, Molecular Neurogenetics Unit, Bethesda, MD 20892.
Ramirez
A N
AN
Gurrola
G B
GB
Nobile
M
M
Prestipino
G
G
Possani
L D
LD
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*
D000911:Antibodies, Monoclonal; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D014118:Toxins, Biological; C052567:noxiustoxin