Structural Basis for DNA Gyrase Interaction with Coumermycin A1.

Fiche publication


Date publication

mars 2019

Journal

Journal of medicinal chemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LAMOUR Valérie


Tous les auteurs :
Vanden Broeck AP, McEwen AG, Chebaro Y, Potier N, Lamour V

Résumé

Coumermycin A1 is a natural aminocoumarin that inhibits the bacterial DNA gyrase, a member of the GHKL proteins superfamily. We report here the first co-crystal 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.

Référence

J. Med. Chem.. 2019 Mar 28;: