@article{1d1a0e477d554949a1898e20db2e7922,
title = "Ancient regulatory role of lysine acetylation in central metabolism",
abstract = "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{\textquoteright}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.",
keywords = "Acetylphosphate, Central metabolism, Enolase, Protein acetylation, Proteomics",
author = "Nakayasu, {Ernesto S.} and Burnet, {Meagan C.} and Walukiewicz, {Hanna E.} and Wilkins, {Christopher S.} and Shukla, {Anil K.} and Shelby Brooks and Plutz, {Matthew J.} and Lee, {Brady D.} and Birgit Schilling and Wolfe, {Alan J.} and Susanne M{\"u}ller and Kirby, {John R.} and Rao, {Christopher V.} and Cort, {John R.} and Payne, {Samuel H.}",
note = "Funding Information: We thank Nathan Baker, Wendy Shaw, Joshua Adkins, and Geremy Clair (Pacific Northwest National Laboratory) for insightful discussions and Nathan Johnson for assistance with figures. This work was supported by the U.S. Department of Energy (DOE), Office of Science, Office of Biological and Environmental Research, Early Career Research Program with additional support from the Pan-omics Program. A.J.W., B.S., C.V.R., and H.E.W were supported by the DOE grant DE-SC0012443. A.J.W., B.S., J.R.K., and S.M. were supported by the NIH/NIAMS grant AI108255. Work was performed in the Environmental Molecular Science Laboratory, a U.S. Department of Energy national scientific user facility at Pacific Northwest National Laboratory (PNNL) in Richland, WA. Battelle operates PNNL for the DOE under contract DE-AC05-76RLO01830. We declare that we have no financial conflicts of interest. Funding Information: This work was supported by the U.S. Department of Energy (DOE), Office of Science, Office of Biological and Environmental Research, Early Career Research Program with additional support from the Pan-omics Program. A.J.W., B.S., C.V.R., and H.E.W were supported by the DOE grant DE-SC0012443. A.J.W., B.S., J.R.K., and S.M. were supported by the NIH/NIAMS grant AI108255. Work was performed in the Environmental Molecular Science Laboratory, a U.S. Department of Energy national scientific user facility at Pacific Northwest National Laboratory (PNNL) in Richland, WA. Battelle operates PNNL for the DOE under contract DE-AC05-76RLO01830. We declare that we have no financial conflicts of interest. Publisher Copyright: {\textcopyright} 2017 Nakayasu et al.",
year = "2017",
month = nov,
day = "1",
doi = "10.1128/mBio.01894-17",
language = "English (US)",
volume = "8",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "6",
}