Characterization of quercetin binding site on DNA gyrase

Biochem Biophys Res Commun. 2003 Jun 27;306(2):530-6. doi: 10.1016/s0006-291x(03)01006-4.


Gyrases are DNA topology modifying enzymes present only in prokaryotes which makes them an attractive target for antibacterial drugs. Quercetin, one of the most abundant natural flavonoids, inhibits supercoiling activity of bacterial gyrase and induces DNA cleavage. It has been generally assumed that the mechanism of flavonoid inhibition is based on interaction with DNA. We show that quercetin binds to the 24 kDa fragment of gyrase B of Escherichia coli with a K(D) value of 15 microM and inhibits ATPase activity of gyrase B. Its binding site overlaps with ATP binding pocket and could be competitively replaced by either ATP or novobiocin. The structural model of quercetin-gyrase complex was prepared, based on the close similarity with ATP and quercetin binding sites of the src family tyrosine kinase Hck. We propose that quercetin inhibits gyrases through two different mechanisms based either on interaction with DNA or with ATP binding site of gyrase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / pharmacology
  • Binding Sites
  • DNA Gyrase / chemistry*
  • Dose-Response Relationship, Drug
  • Escherichia coli / enzymology
  • Flavonoids / chemistry
  • Kinetics
  • Models, Molecular
  • Novobiocin / pharmacology
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / chemistry
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins c-hck
  • Quercetin / chemistry*
  • Spectrometry, Fluorescence
  • Time Factors


  • Flavonoids
  • Proto-Oncogene Proteins
  • Novobiocin
  • Adenosine Triphosphate
  • Quercetin
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-hck
  • Adenosine Triphosphatases
  • DNA Gyrase