Conformational changes in cytochrome c directed by ethylene glycol accompanying complex formation: Protein-solvent preferential interaction or/and kosmotropic effect

Spectrochim Acta A Mol Biomol Spectrosc. 2020 Dec 5:242:118788. doi: 10.1016/j.saa.2020.118788. Epub 2020 Aug 3.

Abstract

When proteins interact with solvent or co-solutes with a high specificity and affinity, protein-ligand complexes may be formed. Such phenomenon may involve the processes like intra- and intermolecular interactions, which result in interaction based protein folding. In this study, cytochrome c (cyt c) was treated with different concentrations of ethylene glycol (EG) in crowded and confined media to check its structural stability using various spectroscopic techniques at pH 7.0 and 25 °C. The various spectroscopic techniques including circular dichroism (Soret, far- and near-UV regions), Fourier transform infrared (FTIR), absorption (UV and visible) and Trp fluorescence shows both secondary and tertiary structure of cyt c increases when treated with EG. The investigations using dynamic light scattering (DLS), time resolved fluorescence and isothermal titration calorimetry (ITC) for binding studies shows weak interaction between EG and cyt c. Small increase in the structure of the protein and insignificant decrease in hydrodynamic radii of the protein was observed from the studies. Molecular docking studies showed that EG has binding site on the protein and interact with few amino acid residues by weak interactions such as van der Waals and hydrogen bonding. This study helps in understanding the protein-ligand interactions, provides facts and the mechanisms that mediates the recognition of binding site for specific ligand to the receptor protein, which make possible of the discovery, design, and development of drugs at molecular level without affecting proteins within an organism.

Keywords: Binding-induced folding; Ethylene glycol; Isothermal titration calorimetry; Molecular docking; Time resolved fluorescence.

MeSH terms

  • Circular Dichroism
  • Cytochromes c*
  • Ethylene Glycol
  • Molecular Docking Simulation
  • Pharmaceutical Preparations*
  • Protein Binding
  • Solvents
  • Spectrometry, Fluorescence
  • Thermodynamics

Substances

  • Pharmaceutical Preparations
  • Solvents
  • Cytochromes c
  • Ethylene Glycol