Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance.

Platform Technology and Science, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.

Nature structural & molecular biology 2010 Sep

filter terms:

Quinolone antibacterials have been used to treat bacterial infections for over 40 years. A crystal structure of moxifloxacin in complex with Acinetobacter baumannii topoisomerase IV now shows the wedge-shaped quinolone stacking between base pairs at the DNA cleavage site and binding conserved residues in the DNA cleavage domain through chelation of a noncatalytic magnesium ion. This provides a molecular basis for the quinolone inhibition mechanism, resistance mutations and invariant quinolone antibacterial structural features.

Citation

Alexandre Wohlkonig, Pan F Chan, Andrew P Fosberry, Paul Homes, Jianzhong Huang, Michael Kranz, Vaughan R Leydon, Timothy J Miles, Neil D Pearson, Rajika L Perera, Anthony J Shillings, Michael N Gwynn, Benjamin D Bax. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nature structural & molecular biology. 2010 Sep;17(9):1152-3