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Ancient Regulatory Role of Lysine Acetylation in Central Metabolism. mBio 2017 11 28;8(6)



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Pubmed Central ID




Scopus ID

2-s2.0-85039922037   31 Citations


Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue's charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggest that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation.IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.

Author List

Nakayasu ES, Burnet MC, Walukiewicz HE, Wilkins CS, Shukla AK, Brooks S, Plutz MJ, Lee BD, Schilling B, Wolfe AJ, Müller S, Kirby JR, Rao CV, Cort JR, Payne SH


John Kirby PhD Chair, Center Associate Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Citric Acid Cycle
Evolution, Molecular
Gene Expression Regulation, Bacterial
Protein Processing, Post-Translational
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0