HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kleerekoper, Q. Articles by Putkey, J. A. Search for Related Content PubMed PubMed Citation Articles by Kleerekoper, Q. Articles by Putkey, J. A. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 34, 23932-23939, August 20, 1999

Drug Binding to Cardiac Troponin C

From the Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77030

Compounds that sensitize cardiac muscle to Ca²⁺ by intervening at the level of regulatory thin filament proteins would have potential therapeutic benefit in the treatment of myocardial infarctions. Two putative Ca²⁺ sensitizers, EMD 57033 and levosimendan, are reported to bind to cardiac troponin C (cTnC). In this study, we use heteronuclear NMR techniques to study drug binding to [methyl-¹³C]methionine-labeled cTnC when free or when complexed with cardiac troponin I (cTnI). In the absence of Ca²⁺, neither drug interacted with cTnC. In the presence of Ca²⁺, one molecule of EMD 57033 bound specifically to the C-terminal domain of free cTnC. NMR and equilibrium dialysis failed to demonstrate binding of levosimendan to free cTnC, and the presence of levosimendan had no apparent effect on the Ca²⁺ binding affinity of cTnC. Changes in the N-terminal methionine methyl chemical shifts in cTnC upon association with cTnI suggest that cTnI associates with the A-B helical interface and the N terminus of the central helix in cTnC. NMR experiments failed to show evidence of binding of levosimendan to the cTnC·cTnI complex. However, levosimendan covalently bound to a small percentage of free cTnC after prolonged incubation with the protein. These findings suggest that levosimendan exerts its positive inotropic effect by mechanisms that do not involve binding to cTnC.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				T. Sorsa, S. Heikkinen, M. B. Abbott, E. Abusamhadneh, T. Laakso, C. Tilgmann, R. Serimaa, A. Annila, P. R. Rosevear, T. Drakenberg, et al. Binding of Levosimendan, a Calcium Sensitizer, to Cardiac Troponin C J. Biol. Chem., March 16, 2001; 276(12): 9337 - 9343. [Abstract] [Full Text] [PDF]

				X. Wang, M. X. Li, L. Spyracopoulos, N. Beier, M. Chandra, R. J. Solaro, and B. D. Sykes Structure of the C-domain of Human Cardiac Troponin C in Complex with the Ca2+ Sensitizing Drug EMD 57033 J. Biol. Chem., June 29, 2001; 276(27): 25456 - 25466. [Abstract] [Full Text] [PDF]