Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Default user image.

Carola Tilgmann

Driftchef

Default user image.

Binding of Levosimendan, a Calcium Sensitizer, to Cardiac Troponin C

Författare

  • Tia Sorsa
  • Sami Heikkinen
  • M. Bret Abbott
  • Ekram Abusamhadneh
  • Tero Laakso
  • Carola Tilgmann
  • Ritva Serimaa
  • Arto Annila
  • Paul R. Rosevear
  • Torbjörn Drakenberg
  • Piero Pollesello
  • Ilkka Kilpeläinen
Visa allt

Summary, in English

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.

Avdelning/ar

  • Kemiska institutionen

Publiceringsår

2001-03-23

Språk

Engelska

Sidor

9337-9343

Publikation/Tidskrift/Serie

Journal of Biological Chemistry

Volym

276

Issue

12

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Biochemistry and Molecular Biology

Ämne

  • Biochemistry and Molecular Biology
  • Pharmaceutical Chemistry

Nyckelord

  • Calcium/metabolism*
  • Magnetic Resonance Spectroscopy
  • Troponin C/metabolism*
  • simendan
  • Myocardium/metabolism*

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0021-9258