Crystal structures of SIRT3 reveal that the α2-α3 loop and α3-helix affect the interaction with long-chain acyl lysine

被引：19

作者：

Gai, Wei ^{[1
,2
]}

Li, He ^{[2
,3
]}

Jiang, Hualiang ^{[2
,4
]}

Long, Yaqiu ^{[2
,3
]}

Liu, Dongxiang ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Dept Pharmacol 3, Beijing 100864, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Beijing 100864, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Mat Med, Drug Design & Dev Ctr, Beijing 100864, Peoples R China

来源：

FEBS LETTERS | 2016年 / 590卷 / 17期

基金：

中国国家自然科学基金;

关键词：

allosteric site; deacylation; inhibitor; long-chain fatty acid; sirtuins; SIRTUINS; INSIGHTS;

D O I：

10.1002/1873-3468.12345

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SIRT1-7 play important roles in many biological processes and age-related diseases. In addition to a NAD(+)-dependent deacetylase activity, they can catalyze several other reactions, including the hydrolysis of long-chain fatty acyl lysine. To study the binding modes of sirtuins to long-chain acyl lysines, we solved the crystal structures of SIRT3 bound to either a H3K9-myristoylated-or a H3K9-palmitoylated peptide. Interaction of SIRT3 with the palmitoyl group led to unfolding of the alpha 3-helix. The myristoyl and palmitoyl groups bind to the C-pocket and an allosteric site near the alpha 3-helix, respectively. We found that the residues preceding the alpha 3-helix determine the size of the C-pocket. The flexibility of the alpha 2-alpha 3 loop and the plasticity of the alpha 3-helix affect the interaction with long-chain acyl lysine.

引用

页码：3019 / 3028

页数：10

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