Exploring Chloride Selectivity and Halogenase Regioselectivity of the SalL Enzyme through Quantum Mechanical/Molecular Mechanical Modeling

The catalytic mechanism of SalL chlorinase has been investigated by combining quantum mechanical/molecular mechanical (QM/MM) techniques and umbrella sampling simulations to compute free energy profiles. Our results shed light on the interesting fact that the substitution of chloride with fluorine i...

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Published inJournal of chemical information and modeling Vol. 60; no. 2; pp. 738 - 746
Main Authors Pereira, Paulo R. M, Araújo, Jéssica de O, Silva, José Rogério A, Alves, Cláudio N, Lameira, Jerônimo, Lima, Anderson H
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 24.02.2020
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Summary:The catalytic mechanism of SalL chlorinase has been investigated by combining quantum mechanical/molecular mechanical (QM/MM) techniques and umbrella sampling simulations to compute free energy profiles. Our results shed light on the interesting fact that the substitution of chloride with fluorine in SalL chlorinase leads to a loss of halogenase activity. The potential of mean force based on DFTB3/MM analysis shows that fluorination corresponds to a barrier 13.5 kcal·mol–1 higher than chlorination. Additionally, our results present a molecular description of SalL acting as a chlorinase instead of a methyl-halide transferase.
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ISSN:1549-9596
1549-960X
DOI:10.1021/acs.jcim.9b01079