Can an external electric field switch between ethylene formation and L-arginine hydroxylation in the ethylene forming enzyme?

The non-heme Fe(II) and 2-oxoglutarate (2OG) dependent ethylene-forming enzyme (EFE) catalyzes both ethylene generation and L-Arg hydroxylation. Despite experimental and computational progress in understanding the mechanism of EFE, no EFE variant has been optimized for ethylene production while simu...

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Bibliographic Details
Published in:Physical chemistry chemical physics : PCCP 2023-05, Vol.25 (19), p.13772-13783
Main Authors: Chaturvedi, Shobhit S, Jaber Sathik Rifayee, Simahudeen Bathir, Ramanan, Rajeev, Rankin, Joel A, Hu, Jian, Hausinger, Robert P, Christov, Christo Z
Format: Article
Language:English
Subjects:
Alanine
Arginine - chemistry
Binding
Electric fields
Electronic structure
Enzyme activity
Enzymes
Ethylene
Ethylenes - chemistry
Ferric Compounds
Hydroxylation
Quantum mechanics
Reaction intermediates
Residues
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Summary:The non-heme Fe(II) and 2-oxoglutarate (2OG) dependent ethylene-forming enzyme (EFE) catalyzes both ethylene generation and L-Arg hydroxylation. Despite experimental and computational progress in understanding the mechanism of EFE, no EFE variant has been optimized for ethylene production while simultaneously reducing the L-Arg hydroxylation activity. In this study, we show that the two L-Arg binding conformations, associated with different reactivity preferences in EFE, lead to differences in the intrinsic electric field (IntEF) of EFE. Importantly, we suggest that applying an external electric field (ExtEF) along the Fe-O bond in the EFE·Fe(III)·OO ˙·2OG·L-Arg complex can switch the EFE reactivity between L-Arg hydroxylation and ethylene generation. Furthermore, we explored how applying an ExtEF alters the geometry, electronic structure of the key reaction intermediates, and the individual energy contributions of second coordination sphere (SCS) residues through combined quantum mechanics/molecular mechanics (QM/MM) calculations. Experimentally generated variant forms of EFE with alanine substituted for SCS residues responsible for stabilizing the key intermediates in the two reactions of EFE led to changes in enzyme activity, thus demonstrating the key role of these residues. Overall, the results of applying an ExtEF indicate that making the IntEF of EFE less negative and stabilizing the off-line binding of 2OG is predicted to increase ethylene generation while reducing L-Arg hydroxylation.
ISSN:1463-9076
1463-9084
DOI:10.1039/d3cp01899g