Biochemical and computational insights of adenosine deaminase inhibition by Epigallocatechin gallate

Comput Biol Chem. 2019 Dec;83:107111. doi: 10.1016/j.compbiolchem.2019.107111. Epub 2019 Aug 17.

Abstract

Epigallocatechin gallate, a flavonoid from Camellia sinensis possess various pharmacological activities such as anticancer, antimicrobial and antioxidant etc. Adenosine deaminase, (ADA), is a key enzyme involved in the purine metabolism, the inhibitors of which is being considered as highly promising candidate for the development of anti-proliferative and anti-inflammatory drugs. In this work we studied adenosine deaminase inhibitory activity of epigallocatechin gallate by using biophysical and computational methods. The enzyme inhibition study result indicated that epigallocatechin gallate possess strong inhibitory activity on ADA. ITC study revealed the energetics of binding. Also the binding is confirmed by using fluorescence spectroscopy. The structural details of binding are obtained from molecular docking and MD simulation studies.

Keywords: Adenosine deaminase; Epigallocatechin gallate; Fluorescence spectroscopy; ITC; Molecular dynamics.

MeSH terms

  • Adenosine Deaminase / metabolism*
  • Adenosine Deaminase Inhibitors / chemistry
  • Adenosine Deaminase Inhibitors / pharmacology*
  • Calorimetry
  • Camellia sinensis / chemistry
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Humans
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Spectrometry, Fluorescence
  • Thermodynamics

Substances

  • Adenosine Deaminase Inhibitors
  • Catechin
  • epigallocatechin gallate
  • Adenosine Deaminase