Molecular Simulations Highlight the Role of Metals in Catalysis and Inhibition of Type II Topoisomerase

none5siType II topoisomerase (topoII) is a metalloenzyme targeted by clinical antibiotics and anticancer agents. Here, we integrate existing structural data with molecular simulation and propose a model for the yet uncharacterized structure of the reactant state of topoII. This model describes a canonical two-metal-ion mechanism and suggests how the metals could rearrange at the catalytic pocket during enzymatic turnover, explaining also experimental evidence for topoII inhibition. These results call for further experimental validation.noneGiulia Palermo;Marco Stenta;Andrea Cavalli;Matteo Dal Peraro;Marco De VivoGiulia Palermo;Marco Stenta;Andrea Cavalli;Matteo Dal Peraro;Marco De Viv