1YC2

Sir2Af2-NAD-ADPribose-nicotinamide

1YC2 の概要

• エントリーDOI: 10.2210/pdb1yc2/pdb
• 分子名称: NAD-dependent deacetylase 2, ADENOSINE-5-DIPHOSPHORIBOSE, ZINC ION, ... (11 entities in total)
• 機能のキーワード: sir2, sirtuin, nicotinamide, nad, adpribose, ternary complex, hydrolase
• 由来する生物種: Archaeoglobus fulgidus
• 細胞内の位置: Cytoplasm (Probable): O30124
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 149541.70

構造登録者

Avalos, J.L.,Bever, M.K.,Wolberger, C. (登録日: 2004-12-21, 公開日: 2005-03-29, 最終更新日: 2024-02-14)

主引用文献

Avalos, J.L.,Bever, K.M.,Wolberger, C.
Mechanism of Sirtuin Inhibition by Nicotinamide: Altering the NAD(+) Cosubstrate Specificity of a Sir2 Enzyme.
Mol.Cell, 17:855-868, 2005

PubMed Abstract: Sir2 enzymes form a unique class of NAD(+)-dependent deacetylases required for diverse biological processes, including transcriptional silencing, regulation of apoptosis, fat mobilization, and lifespan regulation. Sir2 activity is regulated by nicotinamide, a noncompetitive inhibitor that promotes a base-exchange reaction at the expense of deacetylation. To elucidate the mechanism of nicotinamide inhibition, we determined ternary complex structures of Sir2 enzymes containing nicotinamide. The structures show that free nicotinamide binds in a conserved pocket that participates in NAD(+) binding and catalysis. Based on our structures, we engineered a mutant that deacetylates peptides by using nicotinic acid adenine dinucleotide (NAAD) as a cosubstrate and is inhibited by nicotinic acid. The characteristics of the altered specificity enzyme establish that Sir2 enzymes contain a single site that participates in catalysis and nicotinamide regulation and provides additional insights into the Sir2 catalytic mechanism.

PubMed: 15780941
DOI: 10.1016/j.molcel.2005.02.022

実験手法

X-RAY DIFFRACTION (2.4 Å)