4C78

Complex of human Sirt3 with Bromo-Resveratrol and ACS2 peptide

4C78 の概要

• エントリーDOI: 10.2210/pdb4c78/pdb
• 関連するPDBエントリー: 4C7B
• 分子名称: NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-3, MITOCHONDRIAL, ACETYL-COENZYME A SYNTHETASE 2-LIKE, MITOCHONDRIAL, 5-[(E)-2-(4-bromophenyl)ethenyl]benzene-1,3-diol, ... (5 entities in total)
• 機能のキーワード: hydrolase, sirtuin, inhibitor, activation, resveratrol, sirt1, metabolic sensor, metabolism, aging
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Mitochondrion matrix: Q9NTG7 Q9NUB1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33089.29

構造登録者

Nguyen, G.T.T.,Gertz, M.,Weyand, M.,Steegborn, C. (登録日: 2013-09-19, 公開日: 2013-11-20, 最終更新日: 2024-10-16)

主引用文献

Nguyen, G.T.T.,Gertz, M.,Steegborn, C.
Crystal Structures of Sirt3 Complexes with 4'-Bromo-Resveratrol Reveal Binding Sites and Inhibition Mechanism.
Chem.Biol., 20:1375-, 2013

PubMed Abstract: Sirtuins are protein deacetylases regulating aging processes and various physiological functions. Resveratrol, a polyphenol found in red wine, activates human Sirt1 and inhibits Sirt3, and it can mimic calorie restriction effects, such as lifespan extension in lower organisms. The mechanism of Sirtuin modulation by resveratrol is not well understood. We used 4'-bromo-resveratrol (5-(2-(4-hydroxyphenyl)vinyl)-1,3-benzenediol) to study Sirt1 and Sirt3 modulation. Despite its similarity to the Sirt1 activator resveratrol, the compound potently inhibited both, Sirt1 and Sirt3. Crystal structures of Sirt3 in complex with a fluorophore-labeled and with a native substrate peptide, respectively, in presence of 4'-bromo-resveratrol reveal two compound binding sites. Biochemical studies identify the internal site and substrate competition as the mechanism for inhibition, providing a drug target site, and homology modeling suggests that the second, allosteric site might indicate the site for Sirt1 activation.

PubMed: 24211137
DOI: 10.1016/J.CHEMBIOL.2013.09.019

実験手法

X-RAY DIFFRACTION (2 Å)