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

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• 作者：Giulia Palermo ; Marco Stenta ; Andrea Cavalli ; Matteo Dal Peraro ; Marco De Vivo
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：February 12, 2013
• 年：2013
• 卷：9
• 期：2
• 页码：857-862
• 全文大小：406K
• 年卷期：v.9,no.2(February 12, 2013)
• ISSN：1549-9626

文摘

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.