title: Drug binding by calmodulin: crystal structure of a calmodulin-trifluoperazine complex.
abstract: 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.
authors: Department of Pathology, University of Alabama at Birmingham 35294.
authors: W J
authors: WJ
authors: Cook
authors: L J
authors: LJ
authors: Walter
authors: M R
authors: MR
authors: Walter
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000737:chemistry*; D002417:Cattle; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014268:Trifluoperazine / Q000737:chemistry*
chemical_list: D002147:Calmodulin; D014268:Trifluoperazine