title: Refined solution structure of the anti-mammal and anti-insect LqqIII scorpion toxin: comparison with other scorpion toxins.
abstract: The solution structure of the anti-mammal and anti-insect LqqIII toxin from the scorpion Leiurus quinquestriatus quinquestriatus was refined and compared with other long-chain scorpion toxins. This structure, determined by 1H-NMR and molecular modeling, involves an alpha-helix (18-29) linked to a three-stranded beta-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 A for C alpha 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 CS alpha beta (Cysteine Stabilized alpha-helix beta-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.
authors.affiliation: Centre de Biophysique Moléculaire (CNRS), Orléans, France.
authors.forename: C
authors.initials: C
authors.lastname: Landon
authors.forename: P
authors.initials: P
authors.lastname: Sodano
authors.forename: B
authors.initials: B
authors.lastname: Cornet
authors.forename: J M
authors.initials: JM
authors.lastname: Bonmatin
authors.forename: C
authors.initials: C
authors.lastname: Kopeyan
authors.forename: H
authors.initials: H
authors.lastname: Rochat
authors.forename: F
authors.initials: F
authors.lastname: Vovelle
authors.forename: M
authors.initials: M
authors.lastname: Ptak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects; D004331:Drosophila melanogaster / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000187:drug effects; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009498:Neurotoxins; D010455:Peptides; D012604:Scorpion Venoms; D015222:Sodium Channels; D012996:Solutions; C077585:leiurutoxin III