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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