A 113Cd and 1H NMR study of the interaction of calmodulin with D600, trifluoperazine and some other hydrophobic drugs.

Abstract

The interaction of calmodulin with D600 (a methoxy derivative of verapamil), trifluoperazine and some other drugs was studied by 113Cd and 1H NMR. All four cation binding sites of calmodulin were found to be affected by the binding of the drugs to calmodulin. The physiologically active and inactive forms of felodipine were found to give 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 two strongly bound trifluoperazine molecules were found to differ by one or two orders of magnitude. A competition study showed that trifluoperazine replaces D600 from at least one binding site on calmodulin. Moreover the binding of D600 was found to be calcium dependent. The data indicate that two calcium ions bound to calmodulin are sufficient to render the binding site(s) accessible for D600.