An insect-specific toxin from Centruroides noxius Hoffmann. cDNA, primary structure, three-dimensional model and electrostatic surface potentials in comparison with other toxin variants.
Scorpion toxins acting on sodium channels differ in their specificity. Toxic peptides specific towards mammals and arthropods (insects and/or crustaceans) have been described. Because of the similar three-dimensional fold of these peptides, the molecular base of their specificity is thought to reside in certain differences at the level of amino acid residues especially within or near the binding site of the toxin to the particular ion channel. The cDNA, amino acid sequence and biological activity of an insect-specific toxin, Cn10, from the scorpion Centruroides noxius Hoffmann is reported. The electrostatic potential surface around a three-dimensional model of Cn10 was calculated. It revealed that residues Tyr4, Lys13, Ile18, Leu19, Gly20, Lys43, Leu44, Thr57, Tyr58, Pro59, Thr64 and Cys65, situated at the side of the toxin proposed in the literature to bind to the sodium channel, constitute a positive surface region. Therefore, they may form the site that binds to the channel. Cn10 was included in a comparative analysis of two groups of natural variants, highly similar peptides of the genus Centruroides with specificities towards mammals or arthropods. A number of surface-accessible residues, consistently different between the two groups and situated near the putative binding site, may be of importance for the specificity of the analyzed toxins.
Selisko
B
B
Department of Molecular Recognition and Structural Biology, Universidad Nacional Autonoma de Mexico, Cuernavaca, Mexico.
Garcia
C
C
Becerril
B
B
Delepierre
M
M
Possani
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D003400:Astacoidea; D001665:Binding Sites; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006135:Gryllidae; D007473:Ion Channels / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity; D012604:Scorpion Venoms / Q000096:biosynthesis / Q000737:chemistry* / Q000633:toxicity*; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D018076:DNA, Complementary; D007473:Ion Channels; D011994:Recombinant Proteins; D012604:Scorpion Venoms; C103184:toxin 10, Centruroides