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Iberiotoxin (IbTX) is a remarkably selective α-K toxin peptide (α-KTx) inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin inhibits both the maxi-K and KV1.3 channels with similar high affinity. The present study investigates the molecular basis for this specificity through mutagenesis of IbTX. The interactions of mutated peptides with maxi-K and KV1.3 channels were monitored...