5FYQ

Sirt2 in complex with a 13-mer trifluoroacetylated Ran peptide

Summary for 5FYQ

• Entry DOI: 10.2210/pdb5fyq/pdb
• Descriptor: NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-2, RAN AA 31-43, SULFATE ION, ... (5 entities in total)
• Functional Keywords: hydrolase, sirtuin, kdac, lysine-deacetylase, lysine-acetylation, genetic-code expansion
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus. Isoform 1: Cytoplasm . Isoform 2: Cytoplasm . Isoform 5: Cytoplasm : Q8IXJ6; Nucleus : P62826
• Total number of polymer chains: 4
• Total formula weight: 83835.91

Authors

Knyphausen, P.,de Boor, S.,Scislowski, L.,Extra, A.,Baldus, L.,Schacherl, M.,Baumann, U.,Neundorf, I.,Lammers, M. (deposition date: 2016-03-09, release date: 2016-05-25, Last modification date: 2024-01-10)

Primary citation

Knyphausen, P.,De Boor, S.,Kuhlmann, N.,Scislowski, L.,Extra, A.,Baldus, L.,Schacherl, M.,Baumann, U.,Neundorf, I.,Lammers, M.
Insights Into Lysine-Deacetylation of Natively Folded Substrate Proteins by Sirtuins.
J.Biol.Chem., 291:14677-, 2016

PubMed Abstract: 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 acyl chains. Most previous studies investigated sirtuin-catalyzed deacylation on peptide substrates only. We used the genetic code expansion concept to produce natively folded, site-specific, and lysine-acetylated Sirt1-3 substrate proteins, namely Ras-related nuclear, p53, PEPCK1, superoxide dismutase, cyclophilin D, and Hsp10, and analyzed the deacetylation reaction. Some acetylated proteins such as Ras-related nuclear, p53, and Hsp10 were robustly deacetylated by Sirt1-3. However, other reported sirtuin substrate proteins such as cyclophilin D, superoxide dismutase, 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 have implications for the lifetime of acetyl modifications on di-lysine acetylation sites and thus constitute 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.

PubMed: 27226597
DOI: 10.1074/JBC.M116.726307

Experimental method

X-RAY DIFFRACTION (3 Å)