| Abstract: | The solution structure of the anti-mammal and anti-insect LqqIII toxin from the scorpion Leiurus quinquestriatus quinquestriatuswas refined and compared with other long-chain scorpion toxins. This structure, determined by 1H-NMR and molecular modeling, involves an α-helix (18–29) linked to a three-stranded β-sheet (2–6, 33–39, and 43–51) by two disulfide bridges. The average RMSD between the 15 best structures and the mean structure is 0.71 Å for Cα atoms. Comparison between LqqIII, the potent anti-mammal AaHII, and the weakly active variant-3 toxins revealed that the LqqIII three-dimensional structure is closer to that of AaHII than to the variant-3 structure. Moreover, striking analogies were observed between the electrostatic and hydrophobic potentials of LqqIII and AaHII. Several residues are well conserved in long-chain scorpion toxin sequences and seem to be important in protein structure stability and function. Some of them are involved in the CSαβ (Cysteine Stabilized α-helix β-sheet) motif. A comparison between the sequences of the RII rat brain and the Drosophila extracellular loops forming scorpion toxin binding-sites of Na+ channels displays differences in the subsites interacting with anti-mammal or anti-insect toxins. This suggests that hydrophobic as well as electrostatic interactions are essential for the binding and specificity of long-chain scorpion toxins. Proteins 28:360–374, 1997 © 1997 Wiley-Liss, Inc. |
