System-wide identification and prioritization of enzyme substrates by thermal analysis.
Nat Commun
; 12(1): 1296, 2021 02 26.
Article
in En
| MEDLINE
| ID: mdl-33637753
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.
Full text:
1
Database:
MEDLINE
Main subject:
Protein Processing, Post-Translational
/
Enzymes
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Type:
Article
Affiliation country:
Sweden