Structural determinants of scorpion toxin affinity: the charybdotoxin (alpha-KTX) family of K(+)-channel blocking peptides.

Abstract

The structure-activity relationships for the α-K family of K+ channel blockers from scorpion venoms demonstrate the critical contribution of site-directed mutagenesis, electrophysiology, together with three-dimensional information. Additions to the current database of toxin structures should enable us to make increasingly accurate and detailed predictions about the selectivity of channel-toxin interactions from the molecular structure data. Amino acid sequences, alone, cannot provide this information because the sequences provide little information about the location, in 3-dimensional space, of key side-chains relative to the backbone and to each other. In cases when the 3-dimensional structures are known, the use of these α-K toxins has provided a large amount of information about the structure of the outer vestibule of cloned channels. More recently the toxins have been useful in classifying the types of K+ channels that are present in several native preparations.