Carola Tilgmann
Driftchef
Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C : A molecular modelling, fluorescence probe, and proton nuclear magnetic resonance study
Författare
Summary, in English
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.
Publiceringsår
1994-11-18
Språk
Engelska
Sidor
28584-28590
Publikation/Tidskrift/Serie
Journal of Biological Chemistry
Volym
269
Issue
46
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Biochemistry and Molecular Biology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0021-9258