3D4B

Crystal structure of Sir2Tm in complex with Acetyl p53 peptide and DADMe-NAD+

3D4B の概要

• エントリーDOI: 10.2210/pdb3d4b/pdb
• 分子名称: NAD-dependent deacetylase, Acetyl P53 peptide, ZINC ION, ... (5 entities in total)
• 機能のキーワード: rossmann fold, cytoplasm, hydrolase, metal-binding, nad, zinc
• 由来する生物種: Thermotoga maritima
• 細胞内の位置: Cytoplasm (Probable): Q9WYW0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29409.07

構造登録者

Hawse, W.F.,Hoff, K.G.,Fatkins, D.,Daines, A.,Zubkova, O.V.,Schramm, V.L.,Zheng, W.,Wolberger, C. (登録日: 2008-05-14, 公開日: 2008-09-30, 最終更新日: 2024-10-16)

主引用文献

Hawse, W.F.,Hoff, K.G.,Fatkins, D.G.,Daines, A.,Zubkova, O.V.,Schramm, V.L.,Zheng, W.,Wolberger, C.
Structural insights into intermediate steps in the Sir2 deacetylation reaction.
Structure, 16:1368-1377, 2008

PubMed Abstract: Sirtuin enzymes comprise a unique class of NAD(+)-dependent protein deacetylases. Although structures of many sirtuin complexes have been determined, structural resolution of intermediate chemical steps are needed to understand the deacetylation mechanism. We report crystal structures of the bacterial sirtuin, Sir2Tm, in complex with an S-alkylamidate intermediate, analogous to the naturally occurring O-alkylamidate intermediate, and a Sir2Tm ternary complex containing a dissociated NAD(+) analog and acetylated peptide. The structures and biochemical studies reveal critical roles for the invariant active site histidine in positioning the reaction intermediate, and for a conserved phenylalanine residue in shielding reaction intermediates from base exchange with nicotinamide. The new structural and biochemical studies provide key mechanistic insight into intermediate steps of the Sir2 deacetylation reaction.

PubMed: 18786399
DOI: 10.1016/j.str.2008.05.015

実験手法

X-RAY DIFFRACTION (1.9 Å)