title: Structure of trans-resveratrol in complex with the cardiac regulatory protein troponin C.
abstract: Cardiac troponin, a heterotrimeric protein complex that regulates heart contraction, represents an attractive target for the development of drugs for treating heart disease. Cardiovascular diseases are one of the chief causes of morbidity and mortality worldwide. In France, however, the death rate from heart disease is remarkably low relative to fat consumption. This so-called "French paradox" has been attributed to the high level of consumption of wine in France, and the antioxidant trans-resveratrol is thought to be the primary basis for wine's cardioprotective nature. It has been demonstrated that trans-resveratrol increases the myofilament Ca(2+) sensitivity of guinea pig myocytes [Liew, R., Stagg, M. A., MacLeod, K. T., and Collins, P. (2005) Eur. J. Pharmacol. 519, 1-8]; however, the specific mode of its action is unknown. In this study, the structure of trans-resveratrol free and bound to the calcium-binding protein, troponin C, was determined by nuclear magnetic resonance spectroscopy. The results indicate that trans-resveratrol undergoes a minor conformational change upon binding to the hydrophobic pocket of the C-domain of troponin C. The location occupied by trans-resveratrol coincides with the binding site of troponin I, troponin C's natural binding partner. This has been seen for other troponin C-targeting inotropes and implicates the modulation of the troponin C-troponin I interaction as a possible mechanism of action for trans-resveratrol.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Pineda-Sanabria
authors.forename: Ian M
authors.initials: IM
authors.lastname: Robertson
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sykes
mesh_terms: D002316:Cardiotonic Agents / Q000737:chemistry* / Q000378:metabolism*; D017666:Deuterium Oxide / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism*; D019209:Troponin C / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D013267:Stilbenes; D019209:Troponin C; D017666:Deuterium Oxide; D000077185:Resveratrol