Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase

被引：1090

作者：

Du, Jintang ^{[2
]}

Zhou, Yeyun ^{[1
]}

Su, Xiaoyang ^{[2
]}

Yu, Jiu Jiu ^{[3
]}

Khan, Saba ^{[2
]}

Jiang, Hong ^{[2
]}

Kim, Jungwoo ^{[2
]}

Woo, Jimin ^{[2
]}

Kim, Jun Huyn ^{[2
]}

Choi, Brian Hyun ^{[2
]}

He, Bin ^{[2
]}

Chen, Wei ^{[4
]}

Zhang, Sheng ^{[4
]}

Cerione, Richard A. ^{[2
,5
]}

Auwerx, Johan ^{[3
]}

Hao, Quan ^{[1
,6
]}

Lin, Hening ^{[2
]}

机构：

[1] Cornell Univ, Cornell High Energy Synchrotron Source, MacCHESS, Ithaca, NY 14853 USA

[2] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA

[3] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland

[4] Cornell Univ, Prote & Mass Spectrometry Core Facil, Ithaca, NY 14853 USA

[5] Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA

[6] Univ Hong Kong, Dept Physiol, Hong Kong, Hong Kong, Peoples R China

来源：

SCIENCE | 2011年 / 334卷 / 6057期

关键词：

STRUCTURAL BASIS; MALONYL-COA; DEACETYLASES; MECHANISM; INSIGHTS; ACETYLATION; INHIBITION; SIRTUINS; PEPTIDE; CELLS;

D O I：

10.1126/science.1207861

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo.

引用

页码：806 / 809

页数：4

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