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System-wide identification and prioritization of enzyme substrates by thermal analysis

Author

Listed:
  • Amir Ata Saei

    (Karolinska Institutet
    Harvard Medical School)

  • Christian M. Beusch

    (Karolinska Institutet)

  • Pierre Sabatier

    (Karolinska Institutet)

  • Juan Astorga Wells

    (Karolinska Institutet)

  • Hassan Gharibi

    (Karolinska Institutet)

  • Zhaowei Meng

    (Karolinska Institutet)

  • Alexey Chernobrovkin

    (Karolinska Institutet
    Pelago Bioscience AB)

  • Sergey Rodin

    (Karolinska Institutet
    Uppsala University)

  • Katja Näreoja

    (Karolinska Institutet)

  • Ann-Gerd Thorsell

    (Karolinska Institutet)

  • Tobias Karlberg

    (Karolinska Institutet)

  • Qing Cheng

    (Karolinska Institutet)

  • Susanna L. Lundström

    (Karolinska Institutet)

  • Massimiliano Gaetani

    (Karolinska Institutet
    SciLifeLab
    Karolinska Institutet)

  • Ákos Végvári

    (Karolinska Institutet
    Karolinska Institutet)

  • Elias S. J. Arnér

    (Karolinska Institutet)

  • Herwig Schüler

    (Karolinska Institutet)

  • Roman A. Zubarev

    (Karolinska Institutet
    I.M. Sechenov First Moscow State Medical University)

Abstract

Despite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

Suggested Citation

  • Amir Ata Saei & Christian M. Beusch & Pierre Sabatier & Juan Astorga Wells & Hassan Gharibi & Zhaowei Meng & Alexey Chernobrovkin & Sergey Rodin & Katja Näreoja & Ann-Gerd Thorsell & Tobias Karlberg &, 2021. "System-wide identification and prioritization of enzyme substrates by thermal analysis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21540-6
    DOI: 10.1038/s41467-021-21540-6
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    Cited by:

    1. Pierre Sabatier & Christian M. Beusch & Amir A. Saei & Mike Aoun & Noah Moruzzi & Ana Coelho & Niels Leijten & Magnus Nordenskjöld & Patrick Micke & Diana Maltseva & Alexander G. Tonevitsky & Vincent , 2021. "An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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