Open AccessMolecular Simulations Highlight the Role of Metals in Catalysis and Inhibition of Type II Topoisomerase
Author(s) -
Giulia Palermo,
Marco Stenta,
Andrea Cavalli,
Matteo Dal Peraro,
Marco De Vivo
Publication year - 2013
Publication title -
journal of chemical theory and computation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.001
H-Index - 185
eISSN - 1549-9626
pISSN - 1549-9618
DOI - 10.1021/ct300691u
Subject(s) - topoisomerase , chemistry , molecular dynamics , catalysis , mechanism (biology) , combinatorial chemistry , molecular model , enzyme , computational biology , biochemistry , computational chemistry , biology , physics , quantum mechanics
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.