Structural Basis for DNA Gyrase Interaction with Coumermycin A1

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.