title: The first identification of lysine malonylation substrates and its regulatory enzyme.
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.
authors: Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Chao
authors: C
authors: Peng
authors: Zhike
authors: Z
authors: Lu
authors: Zhongyu
authors: Z
authors: Xie
authors: Zhongyi
authors: Z
authors: Cheng
authors: Yue
authors: Y
authors: Chen
authors: Minjia
authors: M
authors: Tan
authors: Hao
authors: H
authors: Luo
authors: Yi
authors: Y
authors: Zhang
authors: Wendy
authors: W
authors: He
authors: Ke
authors: K
authors: Yang
authors: Bernadette M M
authors: BM
authors: Zwaans
authors: Daniel
authors: D
authors: Tishkoff
authors: Linh
authors: L
authors: Ho
authors: David
authors: D
authors: Lombard
authors: Tong-Chuan
authors: TC
authors: He
authors: Junbiao
authors: J
authors: Dai
authors: Eric
authors: E
authors: Verdin
authors: Yang
authors: Y
authors: Ye
authors: Yingming
authors: Y
authors: Zhao
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry; D000918:Antibody Specificity; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008314:Malonates / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry; D010735:Phosphoglycerate Kinase / Q000737:chemistry / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D037761:Sirtuins / Q000737:chemistry / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000906:Antibodies; D029968:Escherichia coli Proteins; D008314:Malonates; D009842:Oligopeptides; D010446:Peptide Fragments; D013386:Succinates; D010735:Phosphoglycerate Kinase; C508544:SIRT5 protein, human; D037761:Sirtuins; D010751:Phosphopyruvate Hydratase; D008239:Lysine