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Unraveling the specificities of the different human methionine sulfoxide reductases

Authors

  • Elien Vandermarliere,

    1. Department of Medical Protein Research, VIB, Ghent, Belgium
    2. Department of Biochemistry, Ghent University, Ghent, Belgium
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  • Bart Ghesquière,

    1. Department of Medical Protein Research, VIB, Ghent, Belgium
    2. Department of Biochemistry, Ghent University, Ghent, Belgium
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    • Current address: Dr. Bart Ghesquière, Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven, Belgium and Laboratory of Angiogenesis & Neurovascular Link, Vesalius Research Center, VIB, B-3000 Leuven, Belgium.

  • Veronique Jonckheere,

    1. Department of Medical Protein Research, VIB, Ghent, Belgium
    2. Department of Biochemistry, Ghent University, Ghent, Belgium
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  • Kris Gevaert,

    Corresponding author
    1. Department of Medical Protein Research, VIB, Ghent, Belgium
    2. Department of Biochemistry, Ghent University, Ghent, Belgium
    • Correspondence: Professor Kris Gevaert, Department of Medical Protein Research, Universiteit Gent–VIB, A. Baertsoenkaai 3, B-9000 Gent, Belgium

      E-mail: kris.gevaert@vib-ugent.be

      Fax: +32 9 264 94 96

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  • Lennart Martens

    1. Department of Medical Protein Research, VIB, Ghent, Belgium
    2. Department of Biochemistry, Ghent University, Ghent, Belgium
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Abstract

The oxidation of free and protein-bound methionine into methionine sulfoxide is a frequently occurring modification caused by ROS. Most organisms express methionine sulfoxide reductases (MSR enzymes) to repair this potentially damaging modification. Humans express three different MSRB enzymes which reside in different cellular compartments. In this study, we have explored the specificity of the human MSRB enzymes both by in silico modeling and by experiments on oxidized peptides. We found that MSRB1 is the least specific MSRB enzyme, which is in agreement with the observation that MSRB1 is the only MSRB enzyme found in the cytosol and the nucleus, and therefore requires a broad specificity to reduce all possible substrates. MSRB2 and MSRB3, which are both found in mitochondria, are more specific but because of their co-occurrence they can likely repair all possible substrates.

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