Issue 44, 2017

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

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

Supplementary files

Article information

Article type
Paper
Submitted
31 Aug 2017
Accepted
25 Oct 2017
First published
31 Oct 2017
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2017,19, 30107-30119

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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