3GLS

Crystal Structure of Human SIRT3

3GLS の概要

• エントリーDOI: 10.2210/pdb3gls/pdb
• 関連するPDBエントリー: 3GLR 3GLT 3GLU
• 分子名称: NAD-dependent deacetylase sirtuin-3, mitochondrial, ZINC ION, TRIETHYLENE GLYCOL, ... (5 entities in total)
• 機能のキーワード: nad dependent deacetylase, sirtuin, apo structure, hydrolase, metal-binding, mitochondrion, nad, polymorphism, transit peptide, zinc
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: Q9NTG7
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 190462.95

構造登録者

Jin, L.,Wei, W.,Jiang, Y.,Peng, H.,Cai, J.,Mao, C.,Dai, H.,Bemis, J.E.,Jirousek, M.R.,Milne, J.C.,Westphal, C.H.,Perni, R.B. (登録日: 2009-03-12, 公開日: 2009-06-16, 最終更新日: 2023-09-06)

主引用文献

Jin, L.,Wei, W.,Jiang, Y.,Peng, H.,Cai, J.,Mao, C.,Dai, H.,Choy, W.,Bemis, J.E.,Jirousek, M.R.,Milne, J.C.,Westphal, C.H.,Perni, R.B.
Crystal Structures of Human SIRT3 Displaying Substrate-induced Conformational Changes.
J.Biol.Chem., 284:24394-24405, 2009

PubMed Abstract: SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets of crystal structures of human SIRT3, an apo-structure with no substrate, a structure with a peptide containing acetyl lysine of its natural substrate acetyl-CoA synthetase 2, a reaction intermediate structure trapped by a thioacetyl peptide, and a structure with the dethioacetylated peptide bound. These structures provide insights into the conformational changes induced by the two substrates required for the reaction, the acetylated substrate peptide and NAD(+). In addition, the binding study by isothermal titration calorimetry suggests that the acetylated peptide is the first substrate to bind to SIRT3, before NAD(+). These structures and biophysical studies provide key insight into the structural and functional relationship of the SIRT3 deacetylation activity.

PubMed: 19535340
DOI: 10.1074/jbc.M109.014928

実験手法

X-RAY DIFFRACTION (2.7 Å)