2NYR

Crystal Structure of Human Sirtuin Homolog 5 in Complex with Suramin

「2FZQ」から置き換えられました

2NYR の概要

• エントリーDOI: 10.2210/pdb2nyr/pdb
• 分子名称: NAD-dependent deacetylase sirtuin-5, ZINC ION, 8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON IC ACID, ... (4 entities in total)
• 機能のキーワード: histone deacetylase, structural genomics, structural genomics consortium, sgc, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: Q9NXA8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60281.14

構造登録者

Min, J.R.,Antoshenko, T.,Allali-Hassani, A.,Dong, A.,Weigelt, J.,Sundstrom, M.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Plotnikov, A.N.,Structural Genomics Consortium (SGC) (登録日: 2006-11-21, 公開日: 2006-12-19, 最終更新日: 2023-08-30)

主引用文献

Schuetz, A.,Min, J.,Antoshenko, T.,Wang, C.L.,Allali-Hassani, A.,Dong, A.,Loppnau, P.,Vedadi, M.,Bochkarev, A.,Sternglanz, R.,Plotnikov, A.N.
Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin.
Structure, 15:377-389, 2007

PubMed Abstract: Sirtuins are NAD(+)-dependent protein deacetylases and are emerging as molecular targets for the development of pharmaceuticals to treat human metabolic and neurological diseases and cancer. To date, several sirtuin inhibitors and activators have been identified, but the structural mechanisms of how these compounds modulate sirtuin activity have not yet been determined. We identified suramin as a compound that binds to human SIRT5 and showed that it inhibits SIRT5 NAD(+)-dependent deacetylase activity with an IC(50) value of 22 microM. To provide insights into how sirtuin function is altered by inhibitors, we determined two crystal structures of SIRT5, one in complex with ADP-ribose, the other bound to suramin. Our structural studies provide a view of a synthetic inhibitory compound in a sirtuin active site revealing that suramin binds into the NAD(+), the product, and the substrate-binding site. Finally, our structures may enable the rational design of more potent inhibitors.

PubMed: 17355872
DOI: 10.1016/j.str.2007.02.002

実験手法

X-RAY DIFFRACTION (2.06 Å)