Fluoroquinolones stimulate the DNA cleavage activity of topoisomerase IV by promoting the binding of Mg2Â + to the second metal binding site

At low Mg2 + concentrations, fluoroquinolones may stimulate the Topo IV-catalyzed strand breakage reaction by promoting Mg2 + binding to metal binding site B through the structural distortion in DNA. As Mg2 + concentration increases, fluoroquinolones may inhibit the religation reaction by either stabilizing Mg2 + at site B or inhibition the binding of Mg2 + to site A. This study provides a molecular basis of how fluoroquinolones stimulate the Topo IV-catalyzed strand breakage reaction by modulating Mg2 + binding.