Lysine is subject to a wide array of regulatory post-translational modifications due to its positively charged ε-amino group side chain. The most prevalent of these are ubiquitination and acetylation, which are highly conserved among prokaryotes and eukaryotes (1,2). Acyl group transfer from the metabolic intermediates acetyl-, succinyl-, malonyl-, glutaryl-, butyryl-, propionyl-, and crotonyl-CoA all neutralize lysine’s positive charge and confer structural alterations affecting substrate protein function. Lysine acetylation is catalyzed by histone acetyltransferases, HATs, using acetyl-CoA as a cofactor (3,4). Deacylation is mediated by histone deacetylases, HDACs 1-11, and NAD-dependent Sirtuins 1-7. Some sirtuins have little to no deacetylase activity, suggesting that they are better suited for other acyl lysine substrates (5).
Sirt5 is a predominantly mitochondrial desuccinylase and demalonylase (5,6). In the absence of a known succinyltransferase, succinylation is likely driven by the concentration of succinyl-CoA and intracellular pH and is subject to metabolic fluctuations (7,8). Protein succinylation is especially prevalent among mitochondrial metabolic proteins and bacteria, further solidifying the evolutionary link between mitochondria and prokaryotes. It often occurs at lysine residues that are alternatively acetylated or ubiquitinated. More than a thousand lysine succinylation sites were identified on hundreds of proteins, including glutamate dehydrogenase (15 sites), malate dehydrogenase, citrate synthase, carbamoyl phosphate synthase 1, and histone proteins (9).
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|30299S||100 µl (10 assays)||