1M2N

Sir2 homologues (D102G/F159A/R170A) mutant-2'-O-acetyl ADP ribose complex

1M2N の概要

• エントリーDOI: 10.2210/pdb1m2n/pdb
• 関連するPDBエントリー: 1M2G 1M2H 1M2J 1M2K
• 分子名称: Silent Information Regulator 2, ZINC ION, 2'-O-ACETYL ADENOSINE-5-DIPHOSPHORIBOSE, ... (4 entities in total)
• 機能のキーワード: protein-ligand complex, gene regulation
• 由来する生物種: Archaeoglobus fulgidus
• 細胞内の位置: Cytoplasm (Probable): O28597
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56195.05

構造登録者

Chang, J.,Cho, Y. (登録日: 2002-06-24, 公開日: 2003-04-08, 最終更新日: 2024-05-29)

主引用文献

Chang, J.H.,Kim, H.C.,Hwang, K.Y.,Lee, J.W.,Jackson, S.P.,Bell, S.D.,Cho, Y.
Structural basis for the NAD-dependent deacetylase mechanism of Sir2
J.BIOL.CHEM., 277:34489-34498, 2003

PubMed Abstract: The NAD-dependent histone/protein deacetylase activity of Sir2 (silent information regulator 2) accounts for its diverse biological roles including gene silencing, DNA damage repair, cell cycle regulation, and life span extension. We provide crystallographic evidence that 2'-O-acetyl ADP-ribose is the reaction product that is formed at the active site of Sir2 from the 2.6-A co-crystal structure of 2'-O-acetyl-ADP-ribose and Sir2 from Archaeoglobus fulgidus. In addition, we show that His-116 and Phe-159 play critical roles in the catalysis and substrate recognition. The conserved Ser-24 and Asp-101 contribute to the stability for NAD binding rather than being directly involved in the catalysis. The crystal structures of wild type and mutant derivatives of Sir2, in conjunction with biochemical analyses of the mutants, provide novel insights into the reaction mechanism of Sir2-mediated deacetylation.

PubMed: 12091395
DOI: 10.1074/jbc.M205460200

実験手法

X-RAY DIFFRACTION (2.6 Å)