Mechanism Of Protein Oxidative Damage That Is Coupled To Long-Range Electron Transfer To High-Valent Haems

Keywords

Charge resonance; Cytochrome; Electron transfer; Ferryl haem; Methionine sulfoxide; Protein radical.

Abstract

In the absence of its substrate, the auto-reduction of the highvalent bis-Fe(IV) state of the dihaem enzyme MauG is coupled to oxidative damage of a methionine residue. Transient kinetic and solvent isotope effect studies reveal that this process occurs via two sequential long-range electron transfer (ET) reactions from methionine to the haems. The first ET is coupled to proton transfer (PT) to the haems from solvent via an ordered water network. The second ET is coupled to PT at the methionine site and occurs during the oxidation of the methionine to a sulfoxide. This process proceeds via Compound I- and Compound II-like haem intermediates. It is proposed that the methionine radical is stabilized by a two-centre three-electron (2c3e) bond. This provides insight into how oxidative damage to proteins may occur without direct contact with a reactive oxygen species, and how that damage can be propagated through the protein.

Publication Date

6-15-2016

Publication Title

Biochemical Journal

Volume

473

Issue

12

Number of Pages

1769-1775

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1042/BCJ20160047

Socpus ID

84975118582 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84975118582

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