Interaction of trifluoperazine with Tetrahymena calmodulin. A 19F NMR study

We have used 19F NMR to study interactions of trifluoperazine (TFP), a potent calmodulin (CaM) antagonist, with Tetrahymena calmodulin (Tet. CaM). Changes in chemical shift and bandwidth of TFP caused by adding Tet. CaM in the presence of excess Ca2+ were much smaller than those by adding porcine CaM. The spectral features of the TFP-Tet. CaM solution in the presence of excess Ca2+ were quite similar to those of the TFP-porcine CaM solution in the absence of Ca2+. The exchange rate of TFP from Tet. CaM was estimated to be nearly 20 s-1. The TFP-Tet. CaM solution in the absence of Ca2+ showed a pronounced pH dependence of the 19F NMR chemical shift, whereas the solution in the presence of excess Ca2+ showed a smaller pH dependence. Thus, it was suggested that TFP is located near a hydrophilic region of the Tet. CaM molecule in the absence of Ca2+, while TFP is located near a hydrophobic region of the Tet. CaM in the presence of excess Ca2+.