A113Cd and 1H NMR Study of the Interaction of Calmodulin with D600, Trifluoperazine and Some Other Hydrophobic Drugs

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Abstract
The interaction of bovine calmodulin with D600 (methoxyverapamil), trifluoperazine and some other drugs was studied by 113Cd and 1H NMR. All 4 cation binding sites of calmodulin were affected by the binding of the drugs to calmodulin. The physiologically active and inactive forms of felodipine gave qualitatively the same changes in the 113Cd NMR spectra of calmodulin. The interpretation of this observation in terms of the physiological relevance of the binding to calmodulin is discussed. The binding constants for the 2 strongly bound trifluoperazine molecules differed by 1 or 2 orders of magnitude. A competition study showed that trifluoperazine replaces D600 from at least 1 binding site on calmodulin. The binding of D600 was Ca2+ dependent. Evidently, two Ca2+ bound to calmodulin are sufficient to render the binding site(s) accessible for D600.