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Issue 27, 2018
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The proportion of Met80-sulfoxide dictates peroxidase activity of human cytochrome c

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Abstract

The peroxidase activity of cytochrome c is proposed to contribute to apoptosis by peroxidation of cardiolipin in the mitochondrial inner membrane. However, cytochrome c heme is hexa-coordinate with a methionine (Met80) on the distal side, stopping it from acting as an efficient peroxidase. The first naturally occurring variant of cytochrome c discovered, G41S, has higher peroxidase activity than wild-type. To understand the basis for this increase and gain insight into the peroxidase activity of wild-type, we have studied wild-type, G41S and the unnatural variant G41T. Through a combined kinetic and mass spectrometric analysis, we have shown that hydrogen peroxide specifically oxidizes Met80 to the sulfoxide. In the absence of substrate this can be further oxidized to the sulfone, leading to a decrease in peroxidase activity. Peroxidase activity can be correlated with the proportion of sulfoxide present and if fully in that form, all variants have the same activity without a lag phase caused by activation of the protein.

Graphical abstract: The proportion of Met80-sulfoxide dictates peroxidase activity of human cytochrome c

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Publication details

The article was received on 29 May 2018, accepted on 17 Jun 2018 and first published on 26 Jun 2018


Article type: Paper
DOI: 10.1039/C8DT02185F
Citation: Dalton Trans., 2018,47, 9128-9135
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    The proportion of Met80-sulfoxide dictates peroxidase activity of human cytochrome c

    R. D. Parakra, T. Kleffmann, G. N. L. Jameson and E. C. Ledgerwood, Dalton Trans., 2018, 47, 9128
    DOI: 10.1039/C8DT02185F

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