The crystal structure of calmodulin (CaM) bound to trifluoperazine (TFP) has
been determined and refined to a resolution of 2.45 A. Only one TFP is bound to
CaM, but that is sufficient to cause distortion of the central alpha-helix and
juxtaposition of the N- and C-terminal domains similar to that seen in
CaM-polypeptide complexes. The drug makes extensive contacts with residues in
the C-terminal domain of CaM but only a few contacts with one residue in the
N-terminal domain. The structure suggests that substrate binding to the
C-terminal domain is sufficient to cause the conformational changes in
calmodulin that lead to activation of its targets.
