Green Tea Catechins Inhibit Bacterial DNA Gyrase by Interaction With Its ATP Binding Site

J Med Chem. 2007 Jan 25;50(2):264-71. doi: 10.1021/jm060817o.

Abstract

Catechins are the main ingredients of green tea extracts and have been shown to possess versatile biological activities, including antimicrobial. We determined that the catechins inhibit bacterial DNA gyrase by binding to the ATP binding site of the gyrase B subunit. In the group of four tested catechins, epigallocatechin gallate (EGCG) had the highest activity, followed by epicatechin gallate (ECG) and epigallocatechin (EGC). Specific binding to the N-terminal 24 kDa fragment of gyrase B was determined by fluorescence spectroscopy and confirmed using heteronuclear two-dimensional NMR spectroscopy of the EGCG-15N-labeled gyrase B fragment complex. Protein residues affected by binding to EGCG were identified through chemical shift perturbation. Molecular docking calculations suggest that the benzopyran ring of EGCG penetrates deeply into the active site while the galloyl moiety anchors it to the cleft through interactions with its hydroxyl groups, which explains the higher activity of EGCG and ECG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphate / chemistry*
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Binding Sites
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • DNA Gyrase / chemistry*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Structure-Activity Relationship
  • Tea*
  • Topoisomerase II Inhibitors*

Substances

  • Anti-Bacterial Agents
  • Tea
  • Topoisomerase II Inhibitors
  • Adenosine Triphosphate
  • Catechin
  • epicatechin gallate
  • epigallocatechin gallate
  • Adenosine Triphosphatases
  • DNA Gyrase
  • gallocatechol