SOLUTION STRUCTURE OF 2 NEW TOXINS FROM THE VENOM OF THE CHINESE SCORPION BUTHUS-MARTENSI LARSCH BLOCKERS OF POTASSIUM CHANNELS

The solution structure of BmTX2 purified from the venom of the Chinese Buthid Buthus martensi has been determined by 2D NMR spectroscopy tec hniques which led to the description of its 3D conformation. The struc ture consists of a triple-stranded beta-sheet connected to a helical s tructure. This helix encompasses 10 residues, from 11 to 20, begins wi th a turn of 3(10) helix, and ends with an alpha helix. The three stra nds of beta sheet comprise residues 2-6, with a bulge covering residue s 4 and 5, 26-29, and 32-35, with a type I' beta turn centered on resi dues 30-31. We also characterized the solution structure of BmTX1. The two toxins which are potent blockers of both large-conductance calciu m-activated potassium channels (BKCa channels) and voltage-gated potas sium channels (Kv1.3) are highly superimposable and possess the same s tructural characteristics. Analysis of these structures allows us to h ypothesize that, besides the main surface of interaction described by the functional map of charybdotoxin, one can expect that the binding o f scorpion toxins on BKCa channels may involve residues on the edge of this surface.