The crystal structure of calmodulin (CaM) bound to trifluoperazine (TFP) has been determined and refined to a resolution of 2.45 Å. Only one TFP is bound to CaM, but that is sufficient to cause distortion of the central α-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. © 1994, American Chemical Society. All rights reserved.
