Files
Abstract
The post-translational modification of acetylation is a form of chemical modification of proteins or small molecules that can rapidly affect a variety of cellular functions and is present in cells from all domains of life. Enzymes called acetyltransferases perform the acetylation reaction through the addition of an acyl group from the small molecule acetyl-CoA and adding it to an amine of a small molecule or protein. Two types of acetylation of amines can occur; first being N-acetylation, where the epsilon associated amine of a lysyl side chain is acetylated. The other form of acetylation being N-acetylation, or addition of an acyl moiety to the primary amine of a small molecule or the N-terminal amine of a peptide chain. N-acetylation can be reversed through the enzymatic activity of NAD+-dependent sirtuin protein lysine deacetylases, that remove the acyl group from the acetyllysine using NAD+ as a co-substrate to generate O-acetyl-ADP-ribose and nicotinamide as byproducts. This work provides new developments in the role acetylation or deacetylation of three specific areas: i) The role of reversible lysine acetylation (RLA) in modulation of a toxin-antitoxin system in S. enterica that contributes to bacterial persistence. ii) Discovery and characterization of a novel N-acetyltransferase, NatA, that modulates the deacetylase activity of the NAD+-dependent sirtuin protein lysine deacetylase CobB in S. enterica. iii) Characterization of the physiological significance of possessing two isoforms of CobB deacetylase in S. enterica, and lastly iv) The discovery and characterization of NatA-mediated N-terminal acetylation of the nucleoid-associated protein HU in S. enterica.