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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

Pollesello, Piero; Ovaskai, Martti; Kaivola, Juha; Tilgmann, Carola LU ; Lundström, Kenneth; Kalkkinen, Nisse; Ulmanen, Ismo; Nissinen, Erkki and Taskinen, Jyrki (1994) In Journal of Biological Chemistry 269(46). p.28584-28590
Abstract

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... (More)

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.

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author
publishing date
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Contribution to journal
publication status
published
in
Journal of Biological Chemistry
volume
269
issue
46
pages
7 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • Scopus:0028172183
ISSN
0021-9258
language
English
LU publication?
no
id
a2bc8a58-ab27-4070-a240-803d00e01762
date added to LUP
2016-04-11 13:22:37
date last changed
2016-07-27 09:35:17
@misc{a2bc8a58-ab27-4070-a240-803d00e01762,
  abstract     = {<p>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 NH<sub>2</sub>-terminal domain of cTnC. Furthermore, NMR studies performed on the NH<sub>2</sub>-terminal fragment of cTnC showed a spatial proximity between levosimendan and Met<sup>81</sup>, Met<sup>85</sup>, and Phe<sup>77</sup> 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 NH<sub>2</sub>-terminal domain. The role of the binding of levosimendan to cTnC in the pharmacological action of this drug in vivo is discussed.</p>},
  author       = {Pollesello, Piero and Ovaskai, Martti and Kaivola, Juha and Tilgmann, Carola and Lundström, Kenneth and Kalkkinen, Nisse and Ulmanen, Ismo and Nissinen, Erkki and Taskinen, Jyrki},
  issn         = {0021-9258},
  language     = {eng},
  month        = {11},
  number       = {46},
  pages        = {28584--28590},
  publisher    = {ARRAY(0x92a8ab8)},
  series       = {Journal of Biological Chemistry},
  title        = {Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C : A molecular modelling, fluorescence probe, and proton nuclear magnetic resonance study},
  volume       = {269},
  year         = {1994},
}