THE GUANIDINIUM TOXIN BINDING-SITE ON THE SODIUM-CHANNEL

Study of TTX and STX toxins and their interaction with cloned Na chann els has led to a molecular model of the toxins' binding site. This mod el is able to explain isoform differences in binding affinity, allowin g prediction of the structures of toxin-resistant channels. It provide s an example of a detailed drug binding site that could serve as an ex ample for drug engineering to improve affinity and specificity. The mo del has also suggested important molecular characteristics of the chan nel's permeation path, providing a wealth of ideas for study of this f undamental biophysical process at the molecular level. The model of th e TTX and STX binding site outlines an approach to resolution of molec ular structure and of certain structure-function relationships, and ex perimentation provoked by the model will assist in improving it.