Formation and structure of the ferryl [Fe=O] in-termediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree

Rugg, G. and Senn, H.M. (2017) Formation and structure of the ferryl [Fe=O] in-termediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree. Physical Chemistry Chemical Physics, 19(44), pp. 30107-30119. (doi:10.1039/C7CP05937J) (PMID:29099125)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Senn, Dr Hans
Authors: Rugg, G., and Senn, H.M.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Physical Chemistry Chemical Physics
Publisher:Royal Society of Chemistry
ISSN:1463-9076
ISSN (Online):1463-9084
Published Online:31 October 2017
Copyright Holders:Copyright © 2017 Owner Societies
First Published:First published in Physical Chemistry Chemical Physics 19(44): 30107-30119
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
518721Engineering and Physical Sciences Doctoral Training Grant 2009-13Mary GoodmanEngineering and Physical Sciences Research Council (EPSRC)EP/P504937/1VPO VICE PRINCIPAL RESEARCH & ENTERPRISE
584861EPSRC Doctoral Training Grant 2011-2015Mary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/J500434/1VPO VICE PRINCIPAL RESEARCH & ENTERPRISE