DRUG-BINDING BY CALMODULIN - CRYSTAL-STRUCTURE OF A CALMODULIN TRIFLUOPERAZINE COMPLEX

The crystal structure of calmodulin (CaM) bound to trifluoperazine (TF P) has been determined and refined to a resolution of 2.45 Angstrom. O nly one TFP is bound to CaM, but that is sufficient to cause distortio n of the central a-helix and juxtaposition of the N- and C-terminal do mains similar to that seen in CaM-polypeptide complexes. The drug make s 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 st ructure suggests that substrate binding to the C-terminal domain is su fficient to cause the conformational changes in calmodulin that lead t o activation of its targets.