The nature of the trifluoperazine binding sites on calmodulin and troponin-C.
We have employed 1H-nuclear magnetic resonance spectroscopy to study the interaction of the drug trifluoperazine with calmodulin and troponin-C. Distinct trifluoperazine-binding sites exist in the N- and C-terminal halves of both proteins. Each site consists of a group of hydrophobic side-chains brought into proximity by the Ca2+-dependent juxtaposition of two alpha-helical segments of the protein, each, in turn, belonging to a different Ca2+-binding site in the protein half. The trifluoperazine-induced inhibition of the biological activating ability of calmodulin appears to result from conformational restrictions conferred upon the protein by the bound drug.
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments; D011487:Protein Conformation; D011817:Rabbits; D014268:Trifluoperazine / Q000378:metabolism*; D014336:Troponin / Q000378:metabolism*; D019209:Troponin C
D002147:Calmodulin; D010446:Peptide Fragments; D014336:Troponin; D019209:Troponin C; D014268:Trifluoperazine; D002118:Calcium