RESUMO
Invited for the cover of this issue are Christoâ Z. Christov and co-workers at Michigan Technological University, University of Oxford, and Michigan State University. The image depicts the oxygen diffusion channel in classâ 7 histone demethylase (PHF8) and ethylene-forming enzyme (EFE) and changes in the enzymes' conformations upon binding. Read the full text of the article at 10.1002/chem.202300138.
Assuntos
Histona Desmetilases , Ácidos Cetoglutáricos , Humanos , Histona Desmetilases/metabolismo , Ácidos Cetoglutáricos/metabolismo , Oxigenases , Oxigênio , Compostos Ferrosos/metabolismo , Fatores de TranscriçãoRESUMO
This study investigates dioxygen binding and 2-oxoglutarate (2OG) coordination by two model non-heme FeII /2OG enzymes: a classâ 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 -OOâ - intermediate in PHF8 and the off-line FeIII -OOâ - intermediate in EFE.