4X3P

Sirt2 in complex with a myristoyl peptide

4X3P の概要

• エントリーDOI: 10.2210/pdb4x3p/pdb
• 関連するPDBエントリー: 4X3O
• 分子名称: NAD-dependent protein deacetylase sirtuin-2, peptide PRO-LYS-LYS-THR-GLY, ZINC ION, ... (7 entities in total)
• 機能のキーワード: sirt2, myristoyl peptide, hydrolase-peptide complex, hydrolase/peptide
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus. Isoform 1: Cytoplasm . Isoform 2: Cytoplasm . Isoform 5: Cytoplasm : Q8IXJ6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35940.68

構造登録者

Wang, Y.,Zhang, W.,Hao, Q. (登録日: 2014-12-01, 公開日: 2016-01-13, 最終更新日: 2024-11-13)

主引用文献

Wang, Y.,Fung, Y.M.E.,Zhang, W.,He, B.,Chung, M.W.H.,Jin, J.,Hu, J.,Lin, H.,Hao, Q.
Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure.
Cell Chem Biol, 24:339-345, 2017

PubMed Abstract: Sirtuins are NAD-dependent deacylases. Previous studies have established two important enzymatic intermediates in sirtuin-catalyzed deacylation, an alkylamidate intermediate I, which is then converted to a bicyclic intermediate II. However, how intermediate II is converted to products is unknown. Based on potent SIRT2-specific inhibitors we developed, here we report crystal structures of SIRT2 in complexes with a thiomyristoyl lysine peptide-based inhibitor and carba-NAD or NAD. Interestingly, by soaking crystals with NAD, we capture a distinct covalent catalytic intermediate (III) that is different from the previously established intermediates I and II. In this intermediate, the covalent bond between the S and the myristoyl carbonyl carbon is broken, and we believe this intermediate III to be the decomposition product of II en route to form the end products. MALDI-TOF data further support the intermediate III formation. This is the first time such an intermediate has been captured by X-ray crystallography and provides more mechanistic insights into sirtuin-catalyzed reactions.

PubMed: 28286128
DOI: 10.1016/j.chembiol.2017.02.007

実験手法

X-RAY DIFFRACTION (1.8 Å)