alpha-neurotoxins from elapid snake venoms and alpha-conotoxins from marine 
snails bind specifically and with high affinity to nicotinic cholinoceptors. 
Although both types of toxin are polypeptides, there is more than a fourfold 
difference in size between the two and no clear sequence homology is evident. A 
systematic computer search of the three-dimensional structure of erabutoxin b 
(an alpha-neurotoxin from the false sea snake Laticauda semifasciata) was 
performed to identify the locality that most closely matched the amino acid 
compositions of the smaller alpha-conotoxins (from the marine snails Conus magus 
and Conus geographus). The area of greatest similarity centered on residue 
position 25 of erabutoxin b, a locale that is conserved throughout the snake 
alpha-neurotoxins and their homologues. Six proteins unrelated to erabutoxin b 
were compared to the alpha-conotoxins to show that the extent of the erabutoxin 
b/alpha-conotoxin match was too high to be coincidental. Homologues of 
erabutoxin b, namely alpha-cobratoxin from Naja naja siamensis and cytotoxin 
VII4 from Naja mossambica mossambica, were also analyzed. The extent of the 
matching with the alpha-conotoxins decreased in the series erabutoxin b greater 
than alpha-cobratoxin greater than cytotoxin VII4, and this also relates the 
order of similarity to the pharmacological properties of the alpha-conotoxins. 
The alpha-conotoxin-like area of the snake alpha-neurotoxins is peripheral to 
the site previously considered important for binding to the cholinoceptor, even 
though it seems to represent the focus of evolutionary convergence between the 
two types of neurotoxin. The area of resemblance does, however, have strong 
associations with the conformational behavior of the snake toxins. Hence, the 
outcome of this study has important consequences for the current ideas on snake 
alpha-neurotoxin structure/activity relationships and the evolutionary origins 
of neurotoxicity.