Dioxygen Activation by Caenorhabditis elegans Ferritin: The Effect of the Second Coordination Sphere on O2 reduction to H2O2

Wainwright, Maddison, Wong, Henrik P. H., Yadav, Rolly, Bradley, Justin M., Le Brun, Nick E., Jameson, Guy N. L., Warwicker, Jim, Sastri, Chivukula V. and de Visser, Sam P. (2026) Dioxygen Activation by Caenorhabditis elegans Ferritin: The Effect of the Second Coordination Sphere on O2 reduction to H2O2. ChemistryEurope. ISSN 2751-4765 (In Press)

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Abstract

Ferritins are important proteins that store and detoxify iron. They contain a diiron active site that can convert dioxygen into hydrogen peroxide. The active site contains many hydrogen bonding interactions and charged residues and hence the precise mechanism is not well defined. In this work a comprehensive computational study using molecular dynamics and quantum mechanics is presented on the structure and reactivity of dioxygen binding at the diiron(II) active site of a ferritin from the worm Caenorhabditis elegans. The molecular dynamics simulation gives a rigid protein structure due to the large number of polar interactions between residues and solvent water molecules. The calculated dioxygen activation is stepwise with two successive proton transfer steps via an iron(III)-hydroperoxo intermediate. The calculations provide novel insight into the role of the strictly conserved near-active site Tyr residue, which appears to be important for hydrogen bonding and positioning of dioxygen into the active site.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
UEA Research Groups:	Faculty of Science > Research Groups > Pharmacology and Biological Chemistry Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Depositing User:	LivePure Connector
Date Deposited:	09 Feb 2026 13:37
Last Modified:	12 Feb 2026 01:32
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101871
DOI:

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