1lin

Publication Abstract from PubMed

Here we show that, as a consequence of binding the drug trifluoperazine, a major conformational movement occurs in Ca(2+)-calmodulin (CaM). The 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 alteration in Ca(2+)-CaM, which is initiated and stabilized by drug binding. This conformational change is similar to that which occurs on the binding of Ca(2+)-CaM to target peptides. Two hydrophobic binding pockets, created by amino acid residues adjacent to Ca(2+)-coordinating residues, form the key recognition sites on Ca(2+)-CaM for both inhibitors and target enzymes.

Trifluoperazine-induced conformational change in Ca(2+)-calmodulin.,Vandonselaar M, Hickie RA, Quail JW, Delbaere LT Nat Struct Biol. 1994 Nov;1(11):795-801. PMID:7634090^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.