The first identification of lysine malonylation substrates and its regulatory enzyme.

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Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y

The first identification of lysine malonylation substrates and its regulatory enzyme.

Mol Cell Proteomics. 2011 Dec;10(12):M111.012658. doi: 10.1074/mcp.M111.012658. Epub 2011 Sep 9.

PubMed ID
21908771 [ View in PubMed
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Abstract

Protein post-translational modifications (PTMs) at the lysine residue, such as lysine methylation, acetylation, and ubiquitination, are diverse, abundant, and dynamic. They play a key role in the regulation of diverse cellular physiology. Here we report discovery of a new type of lysine PTM, lysine malonylation (Kmal). Kmal was initially detected by mass spectrometry and protein sequence-database searching. The modification was comprehensively validated by Western blot, tandem MS, and high-performance liquid chromatography of synthetic peptides, isotopic labeling, and identification of multiple Kmal substrate proteins. Kmal is a dynamic and evolutionarily conserved PTM observed in mammalian cells and bacterial cells. In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo. This result suggests the possibility of nondeacetylation activity of other class III lysine deacetylases, especially those without obvious acetylation protein substrates. Our results therefore reveal a new type of PTM pathway and identify the first enzyme that can regulate lysine malonylation and lysine succinylation status.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Bifunctional glutamate/proline--tRNA ligaseP07814Details
Glyceraldehyde-3-phosphate dehydrogenaseP04406Details
ADP/ATP translocase 2P05141Details
Malate dehydrogenase, mitochondrialP40926Details
Glucose-6-phosphate isomeraseP06744Details
Glycerol kinaseP0A6F3Details
Fructose-bisphosphate aldolase AP04075Details
Heat shock protein HSP 90-betaP08238Details
Fructose-bisphosphate aldolase class 2P0AB71Details
Glyceraldehyde-3-phosphate dehydrogenase AP0A9B2Details
Actin, alpha skeletal muscleP68133Details
Keratin, type II cytoskeletal 8P05787Details
NAD-dependent protein deacylase sirtuin-5, mitochondrialQ9NXA8Details
Phosphoglycerate kinase 1P00558Details
Acyl-CoA-binding proteinP07108Details
Alpha-enolaseP06733Details
60 kDa heat shock protein, mitochondrialP10809Details
10 kDa heat shock protein, mitochondrialP61604Details