Effect of structural modulation of polyphenolic compounds on the inhibition of Escherichia coli ATP synthase

Int J Biol Macromol. 2012 Apr 1;50(3):476-86. doi: 10.1016/j.ijbiomac.2012.01.019. Epub 2012 Jan 20.


In this paper we present the inhibitory effect of a variety of structurally modulated/modified polyphenolic compounds on purified F(1) or membrane bound F(1)F(o)Escherichia coli ATP synthase. Structural modulation of polyphenols with two phenolic rings inhibited ATP synthase essentially completely; one or three ringed polyphenols individually or fused together inhibited partially. We found that the position of hydroxyl and nitro groups plays critical role in the degree of binding and inhibition of ATPase activity. The extended positioning of hydroxyl groups on imino diphenolic compounds diminished the inhibition and abridged position enhanced the inhibition potency. This was contrary to the effect by simple single ringed phenolic compounds where extended positioning of hydroxyl group was found to be effective for inhibition. Also, introduction of nitro group augmented the inhibition on molar scale in comparison to the inhibition by resveratrol but addition of phosphate group did not. Similarly, aromatic diol or triol with rigid or planar ring structure and no free rotation poorly inhibited the ATPase activity. The inhibition was identical in both F(1)F(o) membrane preparations as well as in isolated purified F(1) and was reversible in all cases. Growth assays suggested that modulated compounds used in this study inhibited F(1)-ATPase as well as ATP synthesis nearly equally.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Membrane / enzymology
  • Cell Membrane / metabolism
  • Culture Media / chemistry
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / cytology
  • Escherichia coli / enzymology*
  • Escherichia coli / growth & development
  • Glucose / pharmacology
  • Models, Molecular
  • Polyphenols / chemistry
  • Polyphenols / pharmacology*
  • Protein Conformation
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Proton-Translocating ATPases / chemistry
  • Proton-Translocating ATPases / metabolism
  • Succinic Acid / pharmacology


  • Culture Media
  • Enzyme Inhibitors
  • Polyphenols
  • Succinic Acid
  • Proton-Translocating ATPases
  • Glucose