Structure of trans-Resveratrol in Complex with the Cardiac Regulatory Protein Troponin C

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• 作者：Sandra E. Pineda-Sanabria ; Ian M. Robertson ; Brian D. Sykes
• 刊名：Biochemistry
• 出版年：2011
• 出版时间：March 1, 2011
• 年：2011
• 卷：50
• 期：8
• 页码：1309-1320
• 全文大小：1217K
• 年卷期：v.50,no.8(March 1, 2011)
• ISSN：1520-4995

文摘

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 鈥淔rench paradox鈥?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鈥檚 cardioprotective nature. It has been demonstrated that trans-resveratrol increases the myofilament Ca²⁺ sensitivity of guinea pig myocytes [Liew, R., Stagg, M. A., MacLeod, K. T., and Collins, P. (2005) Eur. J. Pharmacol. 519, 1鈭?]; 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鈥檚 natural binding partner. This has been seen for other troponin C-targeting inotropes and implicates the modulation of the troponin C鈭抰roponin I interaction as a possible mechanism of action for trans-resveratrol.