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Structure‐activity studies of homologues of short chain neurotoxins from Elapid snake venoms
Author(s) -
Harvey A.L.,
Hider R.C.,
Hodges S.J.,
Joubert F.J.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10810.x
Subject(s) - neurotoxin , acetylcholine , acetylcholine receptor , chemistry , naja , venom , biochemistry , receptor , biology , biophysics , pharmacology
1 Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S 5 C 10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata)were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve‐muscle preparations. 2 All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carbachol but had no effect on responses to direct muscle stimulation. CM10 was only about 5 times less potent than the short neurotoxin CM14; S 5 C 10 and CM12 were respectively 30 and 300 times less active. The block induced by the three homologues, but not by the neurotoxins, was readily reversed by washing. 3 CM10 and CM12 had virtually identical cd. spectra which were closely similar to those of the neurotoxins. The spectrum of S 5 C 10 indicated changes in the environment of tyrosine‐25 and in the position of tryptophan‐29. These alterations could distort the 3‐dimensional arrangement of the residues postulated to form the receptor binding site. 4 The results with CM 10 and CM 12 highlight a role for the first loop (residues 6–16) in the binding of neurotoxins to acetylcholine receptors, in addition to the previously postulated reactive site.