Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase

Jintang Du, Yeyun Zhou, Xiaoyang Su, Jiu Jiu Yu, Saba Khan, Hong Jiang, Jungwoo Kim, Jimin Woo, Jun Huyn Kim, Brian Hyun Choi, Bin He, Wei Chen, Sheng Zhang, Richard A. Cerione, Johan Auwerx, Quan Hao, Hening Lin

Research output: Contribution to journalArticle

650 Citations (Scopus)

Abstract

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 (Arg105) and tyrosine residue (Tyr102) 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.

Original languageEnglish (US)
Pages (from-to)806-809
Number of pages4
JournalScience
Volume334
Issue number6057
DOIs
StatePublished - Nov 11 2011

Fingerprint

NAD
Lysine
Sirtuins
Proteins
Carbamyl Phosphate
Biological Phenomena
Post Translational Protein Processing
Tyrosine
Arginine
Mammals
Mass Spectrometry

ASJC Scopus subject areas

  • General

Cite this

Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., ... Lin, H. (2011). Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science, 334(6057), 806-809. https://doi.org/10.1126/science.1207861

Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. / Du, Jintang; Zhou, Yeyun; Su, Xiaoyang; Yu, Jiu Jiu; Khan, Saba; Jiang, Hong; Kim, Jungwoo; Woo, Jimin; Kim, Jun Huyn; Choi, Brian Hyun; He, Bin; Chen, Wei; Zhang, Sheng; Cerione, Richard A.; Auwerx, Johan; Hao, Quan; Lin, Hening.

In: Science, Vol. 334, No. 6057, 11.11.2011, p. 806-809.

Research output: Contribution to journalArticle

Du, J, Zhou, Y, Su, X, Yu, JJ, Khan, S, Jiang, H, Kim, J, Woo, J, Kim, JH, Choi, BH, He, B, Chen, W, Zhang, S, Cerione, RA, Auwerx, J, Hao, Q & Lin, H 2011, 'Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase', Science, vol. 334, no. 6057, pp. 806-809. https://doi.org/10.1126/science.1207861
Du, Jintang ; Zhou, Yeyun ; Su, Xiaoyang ; Yu, Jiu Jiu ; Khan, Saba ; Jiang, Hong ; Kim, Jungwoo ; Woo, Jimin ; Kim, Jun Huyn ; Choi, Brian Hyun ; He, Bin ; Chen, Wei ; Zhang, Sheng ; Cerione, Richard A. ; Auwerx, Johan ; Hao, Quan ; Lin, Hening. / Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. In: Science. 2011 ; Vol. 334, No. 6057. pp. 806-809.
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