Formation and structure of the ferryl [FeO] intermediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree
| Autor: | Hans Martin Senn, G. Rugg |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
chemistry.chemical_classification
Pantetheine Double bond 010405 organic chemistry Decarboxylation Stereochemistry Non haem iron General Physics and Astronomy Substrate (chemistry) Conjugated system 010402 general chemistry 01 natural sciences 0104 chemical sciences QM/MM chemistry.chemical_compound chemistry Physical and Theoretical Chemistry Chemoselectivity |
| Zdroj: | Physical Chemistry Chemical Physics. 19:30107-30119 |
| ISSN: | 1463-9084 1463-9076 |
| DOI: | 10.1039/c7cp05937j |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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