Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C : A molecular modelling, fluorescence probe, and proton nuclear magnetic resonance study
(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
- Pollesello, Piero ; Ovaskai, Martti ; Kaivola, Juha ; Tilgmann, Carola LU ; Lundström, Kenneth ; Kalkkinen, Nisse ; Ulmanen, Ismo ; Nissinen, Erkki and Taskinen, Jyrki
- publishing date
- 1994-11-18
- type
- 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
-
- pmid:7961805
- 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
- 2024-08-10 08:00:26
@article{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 = {{American Society for Biochemistry and Molecular Biology}}, 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}}, }