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


  • Saei A.A.
  • Beusch C.M.
  • Sabatier P.
  • Wells J.A.
  • Gharibi H.
  • Meng Z.
  • Chernobrovkin A.
  • Rodin S.
  • Näreoja K.
  • Thorsell A.G.
  • Karlberg T.
  • Cheng Q.
  • Lundström S.L.
  • Gaetani M.
  • Végvári Á.
  • Arnér E.S.J.
  • Schüler H.
  • Zubarev R.A.
Дата публикации:01.12.2021
Журнал: Nature Communications
БД: Scopus
Ссылка: Scopus

Аннтотация

© 2021, The Author(s). 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.


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