[The effect of various low molecular weight compounds on the cation-binding properties of troponin with the heart].
R N Geguchadze, Nikolay B. Gusev
Abstract
R N Geguchadze, Nikolay B. Gusev
Abstract
Using models of various complexity (isolated troponin C, troponin C-troponin I complex, troponin complex, troponin-tropomyosin complex, myofibrils), the effects of several low molecular weight organic compounds on the Ca(2+)-binding properties of troponin C were investigated. Trifluoperazine, calmidazolium and substance 48/90 increased the affinity of Ca(2+)-specific sites of troponin C both in the case of isolated troponin and in all the complexes under study. Nicardipine had no effect on the cation-binding activity of isolated troponin C, but increased the affinity of the Ca(2+)-binding sites of troponin C in the complex with troponin I. The cardiotonic drugs APP 201-533 and DPI 201-106 had practically no effect on the cation-binding properties of isolated troponin C or of simple complexes of troponin C. At the same time APP 201-533 increased, whereas DPI, 201-106 decreased the affinity of the Ca(2+)-binding sites of troponin C in myofibrils. It is concluded that the effects of the drugs on the cation-binding properties of troponin C depend on the protein-protein interaction with the filament. Studies of physiological activity of low molecular weight organic compounds require a detailed analysis of their effects on the Ca(2+)-binding activity of troponin C included into protein complexes of different complexity.
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Using models of various complexity (isolated troponin C, troponin C-troponin I complex, troponin complex, troponin-tropomyosin complex, myofibrils), the effects of several low molecular weight organic compounds on the Ca(2+)-binding properties of troponin C were investigated. Trifluoperazine, calmidazolium and substance 48/90 increased the affinity of Ca(2+)-specific sites of troponin C both in the case of isolated troponin and in all the complexes under study. Nicardipine had no effect on the cation-binding activity of isolated troponin C, but increased the affinity of the Ca(2+)-binding sites of troponin C in the complex with troponin I. The cardiotonic drugs APP 201-533 and DPI 201-106 had practically no effect on the cation-binding properties of isolated troponin C or of simple complexes of troponin C. At the same time APP 201-533 increased, whereas DPI, 201-106 decreased the affinity of the Ca(2+)-binding sites of troponin C in myofibrils. It is concluded that the effects of the drugs on the cation-binding properties of troponin C depend on the protein-protein interaction with the filament. Studies of physiological activity of low molecular weight organic compounds require a detailed analysis of their effects on the Ca(2+)-binding activity of troponin C included into protein complexes of different complexity.
Key concepts: Troponin C, Troponin, Troponin I, Chemistry, Troponin complex, Myofibril, Troponin T, Biochemistry