Sirt5 is a NAD-dependent Protein Lysine Demalonylase and Desuccinylase

Overview

Journal Science

Specialty Science

Date 2011 Nov 15

PMID 22076378

Citations 654

Authors

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

Affiliations

Soon will be listed here.

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 (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.

Citing Articles

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