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Issue 44, 2017
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Formation and structure of the ferryl [Fe[double bond, length as m-dash]O] intermediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree

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Abstract

To rationalise mechanistically the intriguing regio- and chemoselectivity patterns for different substrates of the non-haem iron/2-oxoglutarate dependent halogenase SyrB2, it is crucial to elucidate the structure of the pivotal [FeIV[double bond, length as m-dash]O] intermediate. We have approached the problem by a combination of classical and QM/MM modelling. We present complete atomistic models of SyrB2 in complex with its native substrate L-threonine as well as L-α-amino butyric acid and L-norvaline (all conjugated to the pantetheine tether), constructed by molecular docking and extensive MD simulations. We evaluate five isomers of the [Fe[double bond, length as m-dash]O] intermediate in these simulations, with a view to identifying likely structures based on a simple “reaction distance” measure. Starting from models of the resting state, we then use QM/MM calculations to investigate the formation of the [Fe[double bond, length as m-dash]O] species for all three substrates, identifying the intermediates along the O2 activation/decarboxylation pathway on the S = 1, 2, and 3 potential-energy surfaces. We find that, despite differences in the detailed course of the reaction, essentially all pathways produce the same [Fe[double bond, length as m-dash]O] structure, in which the oxido is directed away from the substrate.

Graphical abstract: Formation and structure of the ferryl [Fe [[double bond, length as m-dash]] O] intermediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree

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Publication details

The article was received on 31 Aug 2017, accepted on 25 Oct 2017 and first published on 31 Oct 2017


Article type: Paper
DOI: 10.1039/C7CP05937J
Citation: Phys. Chem. Chem. Phys., 2017,19, 30107-30119
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    Formation and structure of the ferryl [Fe[double bond, length as m-dash]O] intermediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree

    G. Rugg and H. M. Senn, Phys. Chem. Chem. Phys., 2017, 19, 30107
    DOI: 10.1039/C7CP05937J

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