TRIFLUOPERAZINE-INDUCED CONFORMATIONAL CHANGE IN CA2-CALMODULIN()

Here we show that, as a consequence of binding the drug trifluoperazin e, a major conformational movement occurs in Ca2+-calmodulin (CaM). Th e tertiary structure changes from an elongated dumb-bell, with exposed hydrophobic surfaces, to a compact globular form which can no longer interact with its target enzymes. It is likely that inactivation of Ca 2+-CaM by trifluoperazine is due to this major tertiary-structural alt eration in Ca2+-CaM, which is initiated and stabilized by drug binding . This conformational change is similar to that which occurs on the bi nding of Ca2+-CaM to target peptides. Two hydrophobic binding pockets, created by amino acid residues adjacent to Ca2+-coordinating residues , form the key recognition sites on Ca2+-CaM for both inhibitors and t arget enzymes.