A computational exploration of the interactions of the green tea polyphenol (-)-Epigallocatechin 3-Gallate with cardiac muscle troponin C

PLoS One. 2013 Jul 29;8(7):e70556. doi: 10.1371/journal.pone.0070556. Print 2013.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Calcium / chemistry
  • Calcium / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / metabolism
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Conformation
  • Myocardial Contraction
  • Myocardium / metabolism
  • Polyphenols / chemistry*
  • Polyphenols / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Tea / chemistry*
  • Troponin C / chemistry*
  • Troponin C / metabolism

Substances

  • Polyphenols
  • Tea
  • Troponin C
  • Catechin
  • epigallocatechin gallate
  • Calcium

Grants and funding

This work made use of the facilities of HECToR, the United Kingdom's national high-performance computing service, which is provided by UoE HPCx Ltd at the University of Edinburgh, Cray Inc and NAG Ltd, and funded by the Office of Science and Technology through Engineering and Physical Sciences Research Council's High End Computing Programme (EPSRC grants EP/F037457/1 and EP/K013831/1). The authors also acknowledge the use of the EPSRC United Kingdom National Service for Computational Chemistry Software at Imperial College London (project CHEM310). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.