Home Health Analysis of Protein Post-Translational Modifications by Mass Spectrometry
Acetylated lysine (Kac) is generated via the addition of an acetyl group to the free ? amine on the lysine side chain. Lysine acetyltransferase enzymes mediate the transfer of the acetyl group, utilizing acetyl-CoA as the donor molecule. Lysine deacetylase enzymes catalyze removal of the acetyl group. These enzymes were originally termed histone deacetylases and histone acetyltrans- ferases but are generally abbreviated to HDAC/KDAC or HAT/KAT since they also catalyze the addition and removal of acetyl groups from nonhistone proteins. The presence of such enzymatic regulation has led researchers to pose
Analysis of Protein Post-Translational Modifications by Mass Spectrometry, First Edition. Edited by John R. Griffiths and Richard D. Unwin.
© 2017 John Wiley & Sons, Inc. Published 2017 by John Wiley & Sons, Inc.
the question of“Acetylation: a regulatory modification to rival phosphorylation?” discussing the functional significance of lysine acetylation . This was due to the identification of lysine acetylation as an enzyme-mediated dynamic process (analogous to kinase/phosphatase) with acetylation sites providing specific recruitment sites via conserved interaction domains. Importantly too, the question was sparked by the recent discovery of novel, nonhistone acetylated proteins that represented a wide range of cellular proteins, including transcription factors, nuclear import factors, and the cytoskeletal protein, a-tubulin. Prior to this, acetylation had been considered to be a histone modification, co-occurring with protein methylation at multiple sites and with other PTMs to provide “marks” for epigenetic (heritable) regulation. Termed the histone code, PTM marks provide a mechanism for transcriptional regulation by determining dynamic transitions between transcriptionally active or transcriptionally silent chromatin states . Today, lysine acetylation is established as a conserved mechanism across species, central to cellular regulation, with acetyl-CoA, the donor of the acetyl group, proposed as a key node or indicator of the cell metabolic state via alterations in protein acetylation patterns, including of metabolic enzymes mediating their activity [2, 4]. Lysine acetylation can also occur via a nonenzymatic acetyl phosphate-dependent mechanism and is proposed to occur when carbon flux exceeds the capacity of the central metabolic pathways, providing a means to regulate carbon flow through central metabolic pathways [4, 9].
Protein acetylation additionally occurs on the N-terminus of proteins. N-terminal acetylation occurs after the removal of initiator methionine residues, with the acetyl moiety transferred from acetyl-CoA to the a-amino group by the action of N-terminal transferase enzyme. Unlike lysine acetylation, N-terminal acetylation is an irreversible modification. It occurs at predominantly the cotranslational level but can also occur as a PTM .
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