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PDBsum entry 2kdh
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Structural protein
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PDB id
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2kdh
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References listed in PDB file
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Key reference
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Title
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Solution structure of human cardiac troponin c in complex with the green tea polyphenol, (-)-Epigallocatechin 3-Gallate.
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Authors
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I.M.Robertson,
M.X.Li,
B.D.Sykes.
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Ref.
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J Biol Chem, 2009,
284,
23012-23023.
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PubMed id
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Abstract
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Heart muscle contraction is regulated by Ca(2+) binding to the thin filament
protein troponin C. In cardiovascular disease, the myofilament response to
Ca(2+) is often altered. Compounds that rectify this perturbation are of
considerable interest as therapeutics. Plant flavonoids have been found to
provide protection against a variety of human illnesses such as cancer,
infection, and heart disease. (-)-Epigallocatechin gallate (EGCg), the prevalent
flavonoid in green tea, modulates force generation in isolated guinea pig hearts
(Hotta, Y., Huang, L., Muto, T., Yajima, M., Miyazeki, K., Ishikawa, N.,
Fukuzawa, Y., Wakida, Y., Tushima, H., Ando, H., and Nonogaki, T. (2006) Eur. J.
Pharmacol. 552, 123-130) and in skinned cardiac muscle fibers (Liou, Y. M., Kuo,
S. C., and Hsieh, S. R. (2008) Pflugers Arch. 456, 787-800; and Tadano, N.,
Yumoto, F., Tanokura, M., Ohtsuki, I., and Morimoto, S. (2005) Biophys. J. 88,
314a). In this study we describe the solution structure of the Ca(2+)-saturated
C-terminal domain of troponin C in complex with EGCg. Moreover, we show that
EGCg forms a ternary complex with the C-terminal domain of troponin C and the
anchoring region of troponin I. The structural evidence indicates that the
binding site of EGCg on the C-terminal domain of troponin C is in the
hydrophobic pocket in the absence of troponin I, akin to EMD 57033. Based on
chemical shift mapping, the binding of EGCg to the C-terminal domain of troponin
C in the presence of troponin I may be to a new site formed by the troponin
C.troponin I complex. This interaction of EGCg with the C-terminal domain of
troponin C.troponin I complex has not been shown with other cardiotonic
molecules and illustrates the potential mechanism by which EGCg modulates heart
contraction.
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