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

Helena Gradišar,†‡ Primož Pristovšek,†‡ Andreja Plaper,§ and Roman Jerala*‡
Laboratory of biotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia, and KRKA Pharmaceutical Company, marjeka cesta 6, 8501 Novo mesto, Slovenia
J. Med. Chem., 2007, 50 (2), pp 264–271
DOI: 10.1021/jm060817o
Publication Date (Web): December 21, 2006
Copyright © 2007 American Chemical Society
†

 These authors contributed equally to this work.

,
‡

 National Institute of Chemistry.

,
§

 KRKA Pharmaceutical Company.

,
*

 To whom correspondence should be addressed. Tel./Fax:  +396 1 4760 335/300. E-mail:  roman.jerala@ki.si.

Abstract

Abstract Image

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.

View: Full Text HTML | Hi-Res PDF

Tools

Accession Codes

History

  • Published In Issue January 25, 2007
  • Received July 12, 2006

Recommend & Share

Related Content

Other ACS content by these authors: