Interaction of trifluoperazine withTetrahymenacalmodulin

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Abstract
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+.