Structural Basis for DNA Gyrase Interaction with Coumermycin A1

J Med Chem. 2019 Apr 25;62(8):4225-4231. doi: 10.1021/acs.jmedchem.8b01928. Epub 2019 Apr 3.


Coumermycin A1 is a natural aminocoumarin that inhibits bacterial DNA gyrase, a member of the GHKL proteins superfamily. We report here the first cocrystal structures of gyrase B bound to coumermycin A1, revealing that one coumermycin A1 molecule traps simultaneously two ATP-binding sites. The inhibited dimers from different species adopt distinct sequence-dependent conformations, alternative to the ATP-bound form. These structures provide a basis for the rational development of coumermycin A1 derivatives for antibiotherapy and biotechnology applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Aminocoumarins / chemistry*
  • Aminocoumarins / metabolism
  • Binding Sites
  • DNA Gyrase / chemistry*
  • DNA Gyrase / metabolism
  • Dimerization
  • Escherichia coli / enzymology
  • Hydrogen Bonding
  • Molecular Dynamics Simulation
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Thermus thermophilus / enzymology


  • Aminocoumarins
  • Protein Subunits
  • Adenosine Triphosphate
  • DNA Gyrase
  • coumermycin