5FYQ

Sirt2 in complex with a 13-mer trifluoroacetylated Ran peptide

5FYQ の概要

• エントリーDOI: 10.2210/pdb5fyq/pdb
• 分子名称: NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-2, RAN AA 31-43, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, sirtuin, kdac, lysine-deacetylase, lysine-acetylation, genetic-code expansion
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus. Isoform 1: Cytoplasm . Isoform 2: Cytoplasm . Isoform 5: Cytoplasm : Q8IXJ6; Nucleus : P62826
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83835.91

構造登録者

Knyphausen, P.,de Boor, S.,Scislowski, L.,Extra, A.,Baldus, L.,Schacherl, M.,Baumann, U.,Neundorf, I.,Lammers, M. (登録日: 2016-03-09, 公開日: 2016-05-25, 最終更新日: 2025-12-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)