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

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, Qing Cheng, Susanna L. Lundström, Massimiliano Gaetani, Ákos Végvári, Elias S. J. Arnér, Herwig Schüler and Roman A. Zubarev ()
Additional contact information
Amir Ata Saei: Karolinska Institutet
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
Sergey Rodin: Karolinska Institutet
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
Ákos Végvári: Karolinska Institutet
Elias S. J. Arnér: Karolinska Institutet
Herwig Schüler: Karolinska Institutet
Roman A. Zubarev: Karolinska Institutet

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21540-6

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DOI: 10.1038/s41467-021-21540-6

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