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Title
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Trifluoperazine-induced conformational change in Ca(2+)-calmodulin.
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Authors
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M.Vandonselaar,
R.A.Hickie,
J.W.Quail,
L.T.Delbaere.
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Ref.
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Nat Struct Biol, 1994,
1,
795-801.
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PubMed id
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Abstract
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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.
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