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Carola Tilgmann

Driftchef

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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

  • Piero Pollesello
  • Martti Ovaskai
  • Juha Kaivola
  • Carola Tilgmann
  • Kenneth Lundström
  • Nisse Kalkkinen
  • Ismo Ulmanen
  • Erkki Nissinen
  • Jyrki Taskinen

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