• Open Access

Activity-Based Probes for Studying the Activity of Flavin-Dependent Oxidases and for the Protein Target Profiling of Monoamine Oxidase Inhibitors

Authors

  • Joanna M. Krysiak,

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria)
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  • Johannes Kreuzer,

    1. Center for Integrated Protein Science CIPSM, Department of Chemistry, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstraße 4, 85747 Garching (Germany)
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  • Prof. Dr. Peter Macheroux,

    1. Institute of Biochemistry, Graz University of Technology, Petersgasse 12, 8010 Graz (Austria)
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  • Prof. Dr. Albin Hermetter,

    1. Institute of Biochemistry, Graz University of Technology, Petersgasse 12, 8010 Graz (Austria)
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  • Prof. Dr. Stephan A. Sieber,

    Corresponding author
    1. Center for Integrated Protein Science CIPSM, Department of Chemistry, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstraße 4, 85747 Garching (Germany)
    • Center for Integrated Protein Science CIPSM, Department of Chemistry, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstraße 4, 85747 Garching (Germany)
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  • Prof. Dr. Rolf Breinbauer

    Corresponding author
    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria)
    • Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria)
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  • We thank Prof. D. E. Edmondson (Emory University, Atlanta (USA)) for the donation of monoamine oxidases, Prof. Dr. W. Berger (Medical University of Vienna, Vienna, Austria) for the donation of human cell lines, and Prof. Dr. R. Zimmermann (Graz University, Graz, Austria) for use of his cell culture facility. We thank Mona Wolff for excellent scientific support. J.M.K. was supported by the Austrian Science Foundation (FWF) grant W901-B05 DK Molecular Enzymology. S.A.S. thanks the DFG (SFB 749, FOR 1406) and ERC (Starting Grant) for financial support. J.M.K. thanks Milagros Aldeco, Dr. Alexandra Binter, Dr. Ute Stemmer, and Venugopal Gudipati for helpful discussions.

Abstract

original image

High profile: New activity-based protein profiling (ABPP) probes have been designed that target exclusively monoamine oxidases A and B within living cells (see picture; FAD=flavin adenine dinucleotide, FMN=flavin monodinucleotide). With these probes it could be shown that the MAO inhibitor deprenyl, which is in clinical use against Parkinson's disease, shows unique protein specificity despite its covalent mechanism of action.

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