The First Identification of Lysine Malonylation Substrates and Its Regulatory Enzyme

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…

• EM
  Ellison Medical Foundation

  Award: AG-NS-0583-09
• EU
  Elsa U. Pardee Foundation
• AF
  American Foundation for Aging Research
• UO
  University of Michigan
• NI
  National Institutes of Health

  Awards: AG000114, T32-AG000114