4UTN

Crystal structure of zebrafish Sirtuin 5 in complex with succinylated CPS1-peptide

4UTN の概要

• エントリーDOI: 10.2210/pdb4utn/pdb
• 関連するPDBエントリー: 4UTR 4UTV 4UTX 4UTZ 4UU7 4UU8 4UUA 4UUB
• 分子名称: NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL, SUCCINYL-CPS1-PEPTIDE, ZINC ION, ... (7 entities in total)
• 機能のキーワード: hydrolase, regulatory enzyme, rossmann-fold, zinc-binding
• 由来する生物種: DANIO RERIO (ZEBRAFISH); 詳細
• 細胞内の位置: Mitochondrion (By similarity): Q6DHI5
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 62425.07

構造登録者

Pannek, M.,Gertz, M.,Steegborn, C. (登録日: 2014-07-21, 公開日: 2014-08-20, 最終更新日: 2024-01-10)

主引用文献

Roessler, C.,Nowak, T.,Pannek, M.,Gertz, M.,Nguyen, G.T.,Scharfe, M.,Born, I.,Sippl, W.,Steegborn, C.,Schutkowski, M.
Chemical Probing of the Human Sirtuin 5 Active Site Reveals its Substrate Acyl Specificity and Peptide-Based Inhibitors.
Angew.Chem.Int.Ed.Engl., 53:10728-, 2014

PubMed Abstract: Sirtuins are NAD(+)-dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD(+) binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X-ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5.

PubMed: 25111069
DOI: 10.1002/ANIE.201402679

実験手法

X-RAY DIFFRACTION (3 Å)