6FLG

Crystal structure of zebrafish Sirtuin 5 in complex with 3(S)-(naphthylthio)succinyl-CPS1 peptide

6FLG の概要

• エントリーDOI: 10.2210/pdb6flg/pdb
• 分子名称: NAD-dependent protein deacylase sirtuin-5, mitochondrial, 3(S)-(naphthylthio)succinyl-CPS1 peptide, ZINC ION, ... (7 entities in total)
• 機能のキーワード: sirtuin 5, inhibitor, deacylase, signaling protein
• 由来する生物種: Danio rerio (Zebrafish); 詳細
• 細胞内の位置: Mitochondrion : Q6DHI5
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 64833.88

構造登録者

Pannek, M.,Steegborn, C. (登録日: 2018-01-25, 公開日: 2018-04-18, 最終更新日: 2024-01-17)

主引用文献

Kalbas, D.,Liebscher, S.,Nowak, T.,Meleshin, M.,Pannek, M.,Popp, C.,Alhalabi, Z.,Bordusa, F.,Sippl, W.,Steegborn, C.,Schutkowski, M.
Potent and Selective Inhibitors of Human Sirtuin 5.
J. Med. Chem., 61:2460-2471, 2018

PubMed Abstract: Sirtuins are protein deacylases that regulate metabolism and stress responses and are implicated in aging-related diseases. Modulators of the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, e.g., for cancer. Selective and potent inhibitors are available for Sirt2, but selective inhibitors for Sirt5 with K values in the low nanomolar range are lacking. We synthesized and screened 3-arylthiosuccinylated and 3-benzylthiosuccinylated peptide derivatives yielding Sirt5 inhibitors with low-nanomolar K values. A biotinylated derivative with this scaffold represents an affinity probe for human Sirt5 that is able to selectively extract this enzyme out of complex biological samples like cell lysates. Crystal structures of Sirt5/inhibitor complexes reveal that the compounds bind in an unexpected manner to the active site of Sirt5.

PubMed: 29494161
DOI: 10.1021/acs.jmedchem.7b01648

実験手法

X-RAY DIFFRACTION (2.5 Å)