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Proton–Electron Transfer to the Active Site Is Essential for the Reaction Mechanism of Soluble Δ9-Desaturase
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SYSNO ASEP 0525592 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Proton–Electron Transfer to the Active Site Is Essential for the Reaction Mechanism of Soluble Δ9-Desaturase Author(s) Bím, Daniel (UOCHB-X) ORCID, RID
Chalupský, Jakub (UOCHB-X) RID, ORCID
Culka, Martin (UOCHB-X) ORCID
Solomon, E. I. (US)
Rulíšek, Lubomír (UOCHB-X) RID, ORCID
Srnec, M. (CZ)Source Title Journal of the American Chemical Society. - : American Chemical Society - ISSN 0002-7863
Roč. 142, č. 23 (2020), s. 10412-10423Number of pages 12 s. Language eng - English Country US - United States Keywords 2nd order perturbation theory ; density functional theory ; carrier protein desaturase Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry R&D Projects EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GJ20-06451Y GA ČR - Czech Science Foundation (CSF) LTAUSA19148 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 UT WOS 000541685800025 EID SCOPUS 85086355292 DOI 10.1021/jacs.0c01786 Annotation A full understanding of the catalytic action of non-heme iron (NHFe) and non-heme diiron (NHFe2) enzymes is still beyond the grasp of contemporary computational and experimental techniques. Many of these enzymes exhibit fascinating chemo-, regio-, and stereoselectivity, in spite of employing highly reactive intermediates which are necessary for activations of most stable chemical bonds. Herein, we study in detail one intriguing representative of the NHFe2 family of enzymes: soluble Δ9 desaturase (Δ9D), which desaturates rather than performing the thermodynamically favorable hydroxylation of substrate. Its catalytic mechanism has been explored in great detail by using QM(DFT)/MM and multireference wave function methods. Starting from the spectroscopically observed 1,2-μ-peroxo diferric P intermediate, the proton–electron uptake by P is the favored mechanism for catalytic activation, since it allows a significant reduction of the barrier of the initial (and rate-determining) H-atom abstraction from the stearoyl substrate as compared to the “proton-only activated” pathway. Also, we ruled out that a Q-like intermediate (high-valent diamond-core bis-μ-oxo-[FeIV]2 unit) is involved in the reaction mechanism. Our mechanistic picture is consistent with the experimental data available for Δ9D and satisfies fairly stringent conditions required by Nature: the chemo-, stereo-, and regioselectivity of the desaturation of stearic acid. Finally, the mechanisms evaluated are placed into a broader context of NHFe2 chemistry, provided by an amino acid sequence analysis through the families of the NHFe2 enzymes. Our study thus represents an important contribution toward understanding the catalytic action of the NHFe2 enzymes and may inspire further work in NHFe(2) biomimetic chemistry. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2021 Electronic address https://pubs.acs.org/doi/10.1021/jacs.0c01786
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