Targeting DNA gyrase

Abstract

The discovery of the peptide DNA gyrase inhibitor microcin B17 (MccB17) in the early 1990s provided a new tool and hope for a novel peptide-based chemical starting point for a new generation of DNA gyrase inhibitors but the definitive mechanism-of-action of MccB17 has remained unknown. This research report [1], by one of the foremost laboratories in this discipline in the world, provides definitive data on the mode of inhibition of MccB17 and possibly opens the door for additional semisynthetic analogue synthesis based on the MccB17 chemotype. In addition, this unique peptide DNA gyrase inhibitor provides a contrast in activity versus quinolones, Ca²⁺-mediated inhibition/cleavage and the bacterial toxin/peptide CcdB.

• bactericidal protein
• CcdB
• DNA cleavage
• DNA gyrase
• double-strand cleavage
• microcin B17
• supercoiling