The active site of potassium (K) channels catalyses the transport of K ions across the plasma membrane, similar to the catalytic function of the active site of an enzyme. Toxins from scorpion venom inhibit K channel activity competing with a K binding site in the selectivity filter of the channel. Using high-resolution solid- state NMR spectroscopy, we showed that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K channel (KcsA- Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involved a combined analysis of chemical shifts and proton-proton distances and demonstrated that solid-state NMR is a sensitive method for analyzing the structure of a membrane protein-inhibitor complex. We propose that structural flexibility of the K channel's active site and the toxin represents an important determinant for the high specificity of toxin-K channel interactions. More recently, we have analyzed the interaction of KcsA-Kv1.3 with a porphyrin ligand which has a rigid and planar structure. This molecule apparently binds to the pore from the side and may be regarded as a non-competitve inhibitor of K channel activity.

ZMNH, Hamburg (O. P., S. H.), Dep. of NMR-Based Struc. Biol., MPI, Göttingen (A.L.; M.B.), Inst. Jean Roche, Marseille (M.F. M.-E.), Dep. Chemistry, Uni. Calif., Berkeley (D.T.)