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Chlorite dismutase (Cld) is one of the rare enzymes capable of forming oxygen-oxygen bonds. Cld has been identified in a very small number of anaerobic bacteria that can use perchlorate as the final electron acceptor in their electron transport/respiration chain. It has been proposed that the catalytic cycle of Cld involves the binding of chlorite to the enzyme's active site, followed by the cleavage of one of the Cl-O bonds, leading to the formation of a high-valent iron-oxo center and a ClO radical/ion, and then a reorientation to the oxygen atom bound to iron, followed by the release of chloride and molecular oxygen. However, direct experimental confirmation of the existence of a chlorite-heme adduct in Cld is still unavailable, nor is it clear what the coordination mode of chlorite is. Moreover, reaction intermediates have not been directly observed in experiments. Previous DFT calculation from us and others have concluded that hemes cannot form stable adducts with chlorite – unlike, e.g., metallacorrins such as cobalamin [1]. This paper reports the results obtained from QM/MM optimization and QM/MM molecular dynamics calculations on the catalytic cycle, revealing compelling computational evidence that a chlorite-heme adduct in Cld is unlikely to be observable experimentally.
Acknowledgements: Funding from the Ministry of Research, Innovation and Digitization (MIPE), as Intermediary Body for the Operational Programme Competitiveness 2014-2020 project code SMIS 2014+ 127725, contract no. 352/390028/23.09.2021, acronym project INSPIRE; the MIPE as Managing Authority for the Smart Growth, Digitalization and Financial Instruments Programme 2021 - 2027 and the Ministry of Research, Innovation and Digitalization as Intermediary Research Body, project code SMIS 2021+ 324771 contract MIPE no. G-2024-71962/23.10.2024 and contract MCID no.390005/23.10.2024, project acronym INSPIRE-II. Computational facilities were provided by UBB under project POC/398/1/1/124155 - co-financed by the European Regional Development Fund (ERDF) through the Competitiveness Operational Program for Romania 2014-2020 and by the CLOUDUT Project, co-funded by the European Fund of Regional Development through the Competitiveness Operational Programme 2014-2020, contract no. 235/2020.
[1] M. Lehene, C. Zagrean-Tuza, S. Iancu, S.-R. Cosma, A. M. V. Brânzanic, R. Silaghi-Dumitrescu, B. Stoean, J. Biol. Inorg. Chem. 2024, 30, 25–34.
