A computational exploration of the interactions of the green tea polyphenol (-)-Epigallocatechin 3-Gallate with cardiac muscle troponin C.
A computational exploration of the interactions of the green tea polyphenol (-)-Epigallocatechin 3-Gallate with cardiac muscle troponin C.
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DOI：
10.1371/journal.pone.0070556
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Molteni C
中科院分区：
文献类型：
--
作者：
Botten D;Fugallo G;Fraternali F;Molteni C
多亏了绿茶中的多酚和植物化学物质，绿茶被认为具有许多健康益处，包括预防心脏病，但其分子水平上的作用机制仍不清楚。在这里，我们通过原子模拟的方法，探索最丰富的绿茶多酚，(-)-表没食子儿茶素没食子酸酯(EGCG)是如何与心肌肌钙蛋白C(CCTnC)的结构C末端区域相互作用的，cCTnC是一种在心脏收缩中发挥重要作用的钙结合蛋白。我们发现EGCG与cCTnC的疏水裂隙结合良好，与溶液核磁共振实验一致。在肌钙蛋白I的锚定区域(cTnI(34-71))存在的情况下，它也与cCTnC结合。这似乎影响了cCTnC和cTnI(34-71)之间相互作用的强度，也抵消了与扩张型心肌病有关的Gly159Asp突变的影响。我们的模拟结果支持EGCG与肌钙蛋白C的C末端结构域的相互作用可能通过与cTnI的锚定结构域的竞争结合或通过影响cCTnC与cTnI之间的相互作用来帮助调节钙信号(34-71)。
Thanks to its polyphenols and phytochemicals, green tea is believed to have a number of health benefits, including protecting from heart disease, but its mechanism of action at the molecular level is still not understood. Here we explore, by means of atomistic simulations, how the most abundant of the green tea polyphenols, (–)-Epigallocatechin 3-Gallate (EGCg), interacts with the structural C terminal domain of cardiac muscle troponin C (cCTnC), a calcium binding protein that plays an important role in heart contractions. We find that EGCg favourably binds to the hydrophobic cleft of cCTnC consistently with solution NMR experiments. It also binds to cCTnC in the presence of the anchoring region of troponin I (cTnI(34–71)) at the interface between the E and H helices. This appears to affect the strength of the interaction between cCTnC and cTnI(34–71) and also counter-acts the effects of the Gly159Asp mutation, related to dilated cardiomyopathy. Our simulations support the picture that EGCg interacting with the C terminal domain of troponin C may help in regulating the calcium signalling either through competitive binding with the anchoring domain of cTnI or by affecting the interaction between cCTnC and cTnI(34–71).
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影响因子：
3.3
作者：
Hamza, A;Zhan, CG
通讯作者：
Zhan, CG
影响因子：
2.2
作者：
Kostin, Shannon F.;McDonald, Debbie E.;McFadden, David W.
通讯作者：
McFadden, David W.
影响因子：
4.8
作者：
Dweck, David;Reynaldo, Daniel P.;Potter, James D.
通讯作者：
Potter, James D.
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
DOI：
10.1073/pnas.202427399
发表时间：
2002-10-01
影响因子：
11.1
作者：
Laio, A;Parrinello, M
通讯作者：
Parrinello, M