Type 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.
Molecular Simulations Highlight the Role of Metals in Catalysis and Inhibition of Type II Topoisomerase / Giulia Palermo;Marco Stenta;Andrea Cavalli;Matteo Dal Peraro;Marco De Vivo. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - STAMPA. - 9:(2013), pp. 857-862. [10.1021/ct300691u]
Molecular Simulations Highlight the Role of Metals in Catalysis and Inhibition of Type II Topoisomerase
CAVALLI, ANDREA;
2013
Abstract
Type 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
