2QQF

Hst2 bound to ADP-HPD and Acetylated histone H4

2QQF の概要

• エントリーDOI: 10.2210/pdb2qqf/pdb
• 関連するPDBエントリー: 2OD7
• 分子名称: NAD-dependent deacetylase HST2, Histone H4, ZINC ION, ... (5 entities in total)
• 機能のキーワード: sir2, hst2, histone deacetylase, sn1, hydrolase, metal-binding, nad, nucleus, repressor, transcription, transcription regulation, zinc
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• 細胞内の位置: Cytoplasm: P53686; Nucleus: P02309
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36713.18

構造登録者

Marmorstein, R.,Sanders, B.D.,Zhao, K.,Slama, J. (登録日: 2007-07-26, 公開日: 2007-10-09, 最終更新日: 2024-10-30)

主引用文献

Sanders, B.D.,Zhao, K.,Slama, J.T.,Marmorstein, R.
Structural basis for nicotinamide inhibition and base exchange in sir2 enzymes.
Mol.Cell, 25:463-472, 2007

PubMed Abstract: The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD(+) at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called "C pocket" binding site for the nicotinamide group of NAD(+). These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors.

PubMed: 17289592
DOI: 10.1016/j.molcel.2006.12.022

実験手法

X-RAY DIFFRACTION (2 Å)