What’s in a covalent bond?

On the role and formation of covalently bound flavin cofactors

Authors

  • Dominic P. H. M. Heuts,

    1.  Laboratory of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands
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  • Nigel S. Scrutton,

    1.  Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, UK
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  • William S. McIntire,

    1.  Molecular Biology Division, Department of Veterans Affairs Medical Center, San Francisco, CA, USA
    2.  Department of Biochemistry & Biophysics, University of California, San Francisco, CA, USA
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  • Marco W. Fraaije

    1.  Laboratory of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands
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M. W. Fraaije, Laboratory of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
Fax: + 31 50 3634165
Tel: + 31 50 3634345
E-mail: m.w.fraaije@rug.nl

Abstract

Many enzymes use one or more cofactors, such as biotin, heme, or flavin. These cofactors may be bound to the enzyme in a noncovalent or covalent manner. Although most flavoproteins contain a noncovalently bound flavin cofactor (FMN or FAD), a large number have these cofactors covalently linked to the polypeptide chain. Most covalent flavin–protein linkages involve a single cofactor attachment via a histidyl, tyrosyl, cysteinyl or threonyl linkage. However, some flavoproteins contain a flavin that is tethered to two amino acids. In the last decade, many studies have focused on elucidating the mechanism(s) of covalent flavin incorporation (flavinylation) and the possible role(s) of covalent protein–flavin bonds. These endeavors have revealed that covalent flavinylation is a post-translational and self-catalytic process. This review presents an overview of the known types of covalent flavin bonds and the proposed mechanisms and roles of covalent flavinylation.

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