5fyq

Publication Abstract from PubMed

Sirtuins are NAD+ dependent lysine-deacylases, regulating a variety of cellular processes. The nuclear Sirt1, the cytosolic Sirt2 and the mitochondrial Sirt3 are robust deacetylases, whereas the other sirtuins have preferences for longer acylchains. Most previous studies investigated sirtuin-catalysed deacylation on peptide substrates only. We used the genetic code expansion concept to produce natively folded site-specifically lysine acetylated Sirt1-3 substrate proteins, namely Ran, p53, PEPCK1, MnSOD, CypD and Hsp10, and analysed the deacetylation reaction. Some acetylated proteins such as Ran, p53 and Hsp10 were robustly deacetylated by Sirt1-3. However, other reported sirtuin substrate proteins such as CypD, MnSOD and PEPCK1, were not deacetylated. Using a structural and functional approach, we describe the ability of Sirt1-3 to deacetylate two adjacent acetylated lysine residues. The dynamics of this process has implications for the lifetime of acetyl-modifications on di-lysine-acetylation sites and thus constitutes a new mechanism for the regulation of proteins by acetylation. Our studies support that, besides the primary sequence-context, the protein structure is a major determinant of sirtuin substrate specificity.

Insights into lysine-deacetylation of natively folded substrate proteins by sirtuins.,Knyphausen P, de Boor S, Kuhlmann N, Scislowski L, Extra A, Baldus L, Schacherl M, Baumann U, Neundorf I, Lammers M J Biol Chem. 2016 May 18. pii: jbc.M116.726307. PMID:27226597^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.