Levosimendan binds to the hydrophobic pocket of the NH2-terminal domain of human cardiac troponin C, modulating the calcium-induced conformational change.
Levosimendan acts as a calcium sensitizer by binding to the hydrophobic pocket of the NH2-terminal domain of cardiac troponin C.
The binding of a new calcium sensitizer, levosimendan, to human cardiac troponin C (cTnC) is described. Fluorescence studies done on dansylated recombinant human cTnC and a site-directed mutant showed that levosimendan modulated the calcium-induced conformational change in cTnC, and revealed the role of Asp-88 in the binding of the drug to the NH2-terminal domain of cTnC. Furthermore, NMR studies performed on the NH2-terminal fragment of cTnC showed a spatial proximity between levosimendan and Met81, Met85, and Phe77 in the drug-protein complex. These data were used to build an optimized model of the drug-protein complex, in which levosimendan binds cTnC at the hydrophobic pocket of the NH2-terminal domain. The role of the binding of levosimendan to cTnC in the pharmacological action of this drug in vivo is discussed.
Pollesello et al. (1994) studied this question. Levosimendan was evaluated on Binding of levosimendan to human cardiac troponin C. Levosimendan binds to the hydrophobic pocket of the NH2-terminal domain of human cardiac troponin C, modulating the calcium-induced conformational change.