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Binding of Levosime...
Binding of Levosimendan, a Calcium Sensitizer, to Cardiac Troponin C
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- Sorsa, Tia (författare)
- University of Helsinki
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- Heikkinen, Sami (författare)
- University of Helsinki
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- Abbott, M. Bret (författare)
- University of Cincinnati
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- Abusamhadneh, Ekram (författare)
- University of Cincinnati
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- Laakso, Tero (författare)
- University of Helsinki
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- Tilgmann, Carola (författare)
- Orion Corporation
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- Serimaa, Ritva (författare)
- University of Helsinki
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- Annila, Arto (författare)
- VTT Technical Research Center of Finland, Espoo
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- Rosevear, Paul R. (författare)
- University of Cincinnati
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- Drakenberg, Torbjörn (författare)
- Lund University,Lunds universitet,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Pollesello, Piero (författare)
- Orion Corporation
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- Kilpeläinen, Ilkka (författare)
- University of Helsinki
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(creator_code:org_t)
- 2001
- 2001
- Engelska 7 s.
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 276:12, s. 9337-9343
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Levosimendan is an inodilatory drug that mediates its cardiac effect by the calcium sensitization of contractile proteins. The target protein of levosimendan is cardiac troponin C (cTnC). In the current work, we have studied the interaction of levosimendan with Ca2+-saturated cTnC by heteronuclear NMR and small angle x-ray scattering. A specific interaction between levosimendan and the Ca2+-loaded regulatory domain of recombinant cTnCC35S was observed. The changes in the NMR spectra of the N-domain of full-length cTnCC35S, due to the binding of levosimendan to the primary site, were indicative of a slow conformational exchange. In contrast, no binding of levosimendan to the regulatory domain of cTnCA-Cys, where all the cysteine residues are mutated to serine, was detected. Moreover, it was shown that levosimendan was in fast exchange on the NMR time scale with a secondary binding site in the C-domain of both cTnCC35S and cTnCA-Cys. The small angle x-ray scattering experiments confirm the binding of levosimendan to Ca2+-saturated cTnC but show no domain-domain closure. The experiments were run in the absence of the reducing agent dithiothreitol and the preservative sodium azide (NaN 3), since we found that levosimendan reacts with these chemicals, commonly used for preparation of NMR protein samples.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Kemiteknik -- Farmaceutisk synteskemi (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Chemical Engineering -- Pharmaceutical Chemistry (hsv//eng)
Nyckelord
- Calcium/metabolism*
- Magnetic Resonance Spectroscopy
- Troponin C/metabolism*
- simendan
- Myocardium/metabolism*
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Sorsa, Tia
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Heikkinen, Sami
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Abbott, M. Bret
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Abusamhadneh, Ek ...
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Laakso, Tero
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Tilgmann, Carola
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visa fler...
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Serimaa, Ritva
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Annila, Arto
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Rosevear, Paul R ...
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Drakenberg, Torb ...
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Pollesello, Pier ...
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Kilpeläinen, Ilk ...
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visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
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- TEKNIK OCH TEKNOLOGIER
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TEKNIK OCH TEKNO ...
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och Kemiteknik
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och Farmaceutisk syn ...
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Journal of Biolo ...
- Av lärosätet
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Lunds universitet