POSITIVELY CHARGED AMINO-ACID-RESIDUES LOCATED SIMILARLY IN SEA-ANEMONE AND SCORPION TOXINS

Specific groups of sea anemone and scorpion toxins compete on the same pharmacological site, on the voltage-gated sodium channel of mammal e xcitable membranes, However, these scorpion and sea anemone toxins are two distinct protein families, Here we purified and sequenced a new s ea anemone toxin, Bg II, highly toxic to mammals and also a less toxic mutant, Bg III. Two Bg II models were determined from sequence homolo gies with two sea anemone toxin two-dimensional NMR structures. Only o ne model conformed to circular dichroism data obtained from Bg II and was compared with an x-ray structure of a scorpion toxin. The comparis on of the two structures shows that 5 amino acid residues are located similarly in the sea anemone toxin and the scorpion toxin. From these 5 residues, 4 are basic residues, constituting two distinct positively charged poles on the surface of these toxins. In the sea anemone muta nt isolated, a negative charge beside one of the positive poles decrea ses the toxicity. These results show that positively charged amino aci d residues could be essential for the activity of these toxins and out line the role of electrostatic bonds in the interaction of sea anemone and scorpion toxins with their receptor.