The amino terminal sequence of several toxins from the venom of the Mexican scorpion Centruroides noxius Hoffmann

Abstract

The soluble venom from the Mexican scorpion Centruroides noxius HOFFMANN was fractionated by Sephadex G-50 chromatography followed by ion exchange separation on carboxymethylcellulose and Bio-Rex 70 columns. Six homogeneous toxins were obtained by this procedure. The amino acid composition and the amino-terminal amino acid sequence was determined for four of them. They are all basic polypeptides with a molecular weight in the order of 7,000, containing from 59 to 65 amino acid residues with four disulphide bridges.

The primary structure of noxiustoxin: A K+ channel blocking peptide, purified from the venom of the scorpion Centruroides noxius Hoffmann

“…Since Noxiustoxin have only six half-cystines and we have no indication of the presence of free thiol groups, we assume that it has only three disulphide bridges instead of four like all the scorpion toxins studied so far. In conclusion, Noxiustoxin is the first polypeptide toxin shown to be specific for potassium channels (14); the first example of a short peptide chain scorpion toxin directed against mammals, and it has a completely different amino acid sequence, when compared with sequences of more than 39 purified toxins (17,18,20,21) known to be present in purified toxins from the venom of scorpions from all over the world.…”

“…The collection of scorpions from Nayarit, Mexico, the preparation of the soluble venom, the chromatographic resins, the reagents and solvents were all the same as previously described (17). Similarly the lethality of the different fractions and pure toxins were followed according to our previous publication (17).…”

“…The methodology followed for automated ED-MAN degradation and identification of the derivatized PTH-amino acids was identical to the procedure described previously (9,17,18,22).…”

“…The sample used for sequencing was obtained from the three peak-tubes of fraction 11 from Figure 2 of the preceeding publication (17). Actually this material was a common pool from two independent runs.…”

“…Until recently, the great majority of the scorpion toxins were known to be polypeptides with molecular weights in the order of 7,000, composed of 57 to 66 amino acid residues cross-linked by four disulphide bridges (1,12,17,21) with a specificity directed towards the sodium channel (3,6,7,8,10,13,15). These toxins bind to excitable membranes only when the membrane is polarized (6).…”