Drug Binding by Calmodulin: Crystal Structure of a Calmodulin-Trifluoperazine Complex

Academic Article

Abstract

  • 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.
  • Published In

  • Biochemistry  Journal
  • Digital Object Identifier (doi)

    Author List

  • Cook WJ; Walter LJ; Walter MR
  • Start Page

  • 15259
  • End Page

  • 15265
  • Volume

  • 33
  • Issue

  • 51