Isolation, characterization and comparison of a novel crustacean toxin with a mammalian toxin from the venom of the scorpion Centruroides noxius Hoffmann.
A novel crustacean-specific toxin, Cn5, containing 66 amino acid residues was isolated from the venom of the scorpion Centruroides noxius Hoffmann. It is stabilized by four disulfide bridges, formed between Cys12-Cys65, Cys16-Cys41, Cys25-Cys46 and Cys29-Cys48. Toxicity tests revealed that Cn5 is a toxin that affects arthropods but not mammals. However, at high concentrations, Cn5 does displace the mammal-specific toxin Cn2 from rat brain synaptosomes. The concentration of Cn5 that produces half-maximal inhibition (IC50) was estimated to be 100 microM. Sequence comparison of Cn5 with toxin Cn2, a mammal-specific toxin from the same scorpion, showed the presence of two sequence stretches, at positions 30 to 38 and 49 to 58, where the majority of the differences are concentrated. On the three-dimensional structure of Cn5 it is demonstrated that these two sequence stretches form a continuous surface region near the site thought to bind to the sodium channel. We assume that this region might be implicated in determining species specificity.
García
C
C
Department of Molecular Recognition and Structural Biology, National Autonomous University of Mexico, Avenida Universidad, Cuernavaca, Morelos, Mexico.
Becerril
B
B
Selisko
B
B
Delepierre
M
M
Possani
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D003400:Astacoidea; D001921:Brain / Q000378:metabolism; D003445:Crustacea / Q000187:drug effects*; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008322:Mammals; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D012605:Scorpions / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D004220:Disulfides; D012604:Scorpion Venoms; C105894:crustacean-specific toxin 5, Centruroides; C103184:toxin 10, Centruroides; C072990:toxin 2, Centruroides noxius