The Causes and Consequences of Nonenzymatic Protein Acylation.
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Authors
James, Andrew M
Smith, Cassandra L
Smith, Anthony C
Robinson, Alan J
Hoogewijs, Kurt
Murphy, Michael P
Publication Date
2018-11Journal Title
Trends Biochem Sci
ISSN
0968-0004
Publisher
Elsevier BV
Volume
43
Issue
11
Pages
921-932
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
James, A. M., Smith, C. L., Smith, A. C., Robinson, A. J., Hoogewijs, K., & Murphy, M. P. (2018). The Causes and Consequences of Nonenzymatic Protein Acylation.. Trends Biochem Sci, 43 (11), 921-932. https://doi.org/10.1016/j.tibs.2018.07.002
Abstract
Thousands of protein acyl modification sites have now been identified in vivo. However, at most sites the acylation stoichiometry is low, making functional enzyme-driven regulation in the majority of cases unlikely. As unmediated acylation can occur on the surface of proteins when acyl-CoA thioesters react with nucleophilic cysteine and lysine residues, slower nonenzymatic processes likely underlie most protein acylation. Here, we review how nonenzymatic acylation of nucleophilic lysine and cysteine residues occurs; the factors that enhance acylation at particular sites; and the strategies that have evolved to limit protein acylation. We conclude that protein acylation is an unavoidable consequence of the central role of reactive thioesters in metabolism. Finally, we propose a hypothesis for why low-stoichiometry protein acylation is selected against by evolution and how it might contribute to degenerative processes such as aging.
Keywords
Acyl Coenzyme A, Acylation, Animals, Cysteine, Humans, Lysine, Protein Processing, Post-Translational, Proteins
Sponsorship
Medical Research Council (MC_UU_00015/3)
Wellcome Trust (110159/Z/15/Z)
Medical Research Council (MC_U105663142)
Medical Research Council (MC_U105674181)
Identifiers
External DOI: https://doi.org/10.1016/j.tibs.2018.07.002
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287070
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