Dioxygen Binding Is Controlled by the Protein Environment in Non-heme FeII and 2-Oxoglutarate Oxygenases: A Study on Histone Demethylase PHF8 and an Ethylene-Forming Enzyme
Document Type
Article
Publication Date
1-26-2023
Department
Department of Chemistry; Department of Chemical Engineering; Department of Biological Sciences
Abstract
This study investigates dioxygen binding and 2-oxoglutarate (2OG) coordination by two model non-heme FeII/2OG enzymes: a class 7 histone demethylase (PHF8) that catalyzes the hydroxylation of its H3K9me2 histone substrate leading to demethylation reactivity and the ethylene-forming enzyme (EFE), which catalyzes two competing reactions of ethylene generation and substrate l-Arg hydroxylation. Although both enzymes initially bind 2OG by using an off-line 2OG coordination mode, in PHF8, the substrate oxidation requires a transition to an in-line mode, whereas EFE is catalytically productive for ethylene production from 2OG in the off-line mode. We used classical molecular dynamics (MD), quantum mechanics/molecular mechanics (QM/MM) MD and QM/MM metadynamics (QM/MM-MetD) simulations to reveal that it is the dioxygen binding process and, ultimately, the protein environment that control the formation of the in-line FeIII-OO⋅− intermediate in PHF8 and the off-line FeIII-OO⋅− intermediate in EFE.
Publication Title
Chemistry - A European Journal
Recommended Citation
Chaturvedi, S.,
Thomas, M.,
Rifayee, S.,
White, W.,
Wildey, J.,
Warner, C.,
Schofield, C.,
Hu, J.,
Hausinger, R.,
Karabencheva-Christova, T.,
&
Christov, C.
(2023).
Dioxygen Binding Is Controlled by the Protein Environment in Non-heme FeII and 2-Oxoglutarate Oxygenases: A Study on Histone Demethylase PHF8 and an Ethylene-Forming Enzyme.
Chemistry - A European Journal.
http://doi.org/10.1002/chem.202300138
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/16906