1H-NMR Studies of Calmodulin: The Modifying Effect of W-7 (N-(6-Aminohexyl)-5-Chloro-1-Naphthalenesulfonamide) on the Calcium-Induced Conformational Changes of Calmodulin

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Abstract
The effect of W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide), a calmodulin antagonist, on the calcium-bound conformation of calmodulin was studied by 1H-NMR at 400 MHz. W-7 affected the resonances of IIe-27, Phe-68, Phe-92, IIe-100, His-107 and Val-142. The resonances of Met-71, Met-72, Met-76, Phe-89 and Phe-141 may be affected by W-7. These findings suggest that W-7 binds to hydrophobic amino acid residues, which almost occur in calcium-binding sites II, III and IV or their vicinity. The affect of W-7 on the structure of calmodulin was similar to that of other drugs, trifluoperazine, D600 and oxmetidine. Thus, those residues in the high-field methyl region, the methionine methyl region and the phenylalanine aromatic region of calmodulin, which were similarly affected by all four drugs, may be important at the interface for binding of calmodulin to the regulatory sites on target enzymes.