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Mechanism of protein oxidative damage that is coupled to long-range electron transfer to high-valent haems.

ABSTRACT: In the absence of its substrate, the auto-reduction of the high-valent 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.

SUBMITTER: Ma Z

PROVIDER: S-EPMC4903885 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Mechanism of protein oxidative damage that is coupled to long-range electron transfer to high-valent haems.

Ma Zhongxin Z Williamson Heather R HR Davidson Victor L VL

The Biochemical journal 20160413 12

In the absence of its substrate, the auto-reduction of the high-valent 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 ...[more]

PMID: 27076451

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