2H4H

Sir2 H116Y mutant-p53 peptide-NAD

2H4H の概要

• エントリーDOI: 10.2210/pdb2h4h/pdb
• 関連するPDBエントリー: 2H4F
• 分子名称: NAD-dependent deacetylase, Cellular tumor antigen p53, ZINC ION, ... (5 entities in total)
• 機能のキーワード: rossmann fold, zn-binding domain, hydrolase
• 由来する生物種: Thermotoga maritima; 詳細
• 細胞内の位置: Cytoplasm (Probable): Q9WYW0; Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: Q9NP68
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30463.17

構造登録者

Hoff, K.G.,Avalos, J.L.,Sens, K.,Wolberger, C. (登録日: 2006-05-24, 公開日: 2006-09-05, 最終更新日: 2024-11-13)

主引用文献

Hoff, K.G.,Avalos, J.L.,Sens, K.,Wolberger, C.
Insights into the Sirtuin Mechanism from Ternary Complexes Containing NAD(+) and Acetylated Peptide.
Structure, 14:1231-1240, 2006

PubMed Abstract: Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD+ cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD+ and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a conformation different from that seen in previous structures, exposing the alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts with the catalytic histidine. We also present the structure of Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken together, these structures suggest a mechanism for nicotinamide cleavage in which an invariant phenylalanine plays a central role in promoting formation of the O-alkylamidate reaction intermediate and preventing nicotinamide exchange.

PubMed: 16905097
DOI: 10.1016/j.str.2006.06.006

実験手法

X-RAY DIFFRACTION (1.99 Å)