E Abusamhadneh, M B Abbott, A Dvoretsky, N Finley, S Sasi, P R Rosevear
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, College of Medicine, 231 Albert B. Sabin Way, Cincinnati, OH 45267, USA.
FEBS letters 2001 Sep 28We have investigated the binding of bepridil to calcium-saturated cardiac troponin C in a cardiac troponin C/troponin I complex. Nuclear magnetic resonance spectroscopy and [(15)N,(2)H]cardiac troponin C permitted the mapping of bepridil-induced amide proton chemical shifts. A single bepridil-binding site in the regulatory domain was found with an affinity constant of approximately 140 microM(-1). In the presence of cardiac troponin I, bepridil binding to the C domain of cardiac troponin C was not detected. The pattern of bepridil-induced chemical shifts is consistent with stabilization of more open regulatory domain conformational states. A similar pattern of chemical shift perturbations was observed for interaction of the troponin I cardiac-specific amino-terminus with the cardiac troponin C regulatory domain. These results suggest that both bepridil and the cardiac-specific amino-terminus may mediate an increase in calcium affinity by interacting with and stabilizing open regulatory domain conformations. Chemical shift mapping suggests a possible role for inactive calcium-binding site I in the modulation of calcium affinity.
E Abusamhadneh, M B Abbott, A Dvoretsky, N Finley, S Sasi, P R Rosevear. Interaction of bepridil with the cardiac troponin C/troponin I complex. FEBS letters. 2001 Sep 28;506(1):51-4
PMID: 11591369
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