Chemical Reporter for Lysine Malonylation

  • Xiucong BaoEmail author
Part of the Springer Theses book series (Springer Theses)


Lysine malonylation (Kmal), a covalent modification of protein with a malonyl group incorporated at the ε-amine group of lysine through an amide bond (Fig. 2.1), was recently identified as a new PTM based on two different approaches [1, 2].


  1. 1.
    Du J et al (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806–809.
  2. 2.
    Peng C et al (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics MCP 10(M111):012658. Scholar
  3. 3.
    Thinon E, Hang HC (2015) Chemical reporters for exploring protein acylation. Biochem Soc Trans 43:253–261. Scholar
  4. 4.
    Peng T, Hang HC (2015) Bifunctional fatty acid chemical reporter for analyzing S-palmitoylated membrane protein-protein interactions in mammalian cells. J Am Chem Soc 137:556–559. Scholar
  5. 5.
    Hang HC, Wilson JP, Charron G (2011) Bioorthogonal chemical reporters for analyzing protein lipidation and lipid trafficking. Acc Chem Res 44:699–708. Scholar
  6. 6.
    Charron G, Tsou LK, Maguire W, Yount JS, Hang HC (2011) Alkynyl-farnesol reporters for detection of protein S-prenylation in cells. Mol BioSyst 7:67–73. Scholar
  7. 7.
    DeGraw AJ, Palsuledesai C, Ochocki JD, Dozier JK, Lenevich S, Rashidian M, Distefano MD (2010) Evaluation of alkyne-modified isoprenoids as chemical reporters of protein prenylation. Chem Biol Drug Des 76:460–471. Scholar
  8. 8.
    Charron G, Zhang MM, Yount JS, Wilson J, Raghavan AS, Shamir E, Hang HC (2009) Robust fluorescent detection of protein fatty-acylation with chemical reporters. J Am Chem Soc 131:4967–4975. Scholar
  9. 9.
    Zaro BW, Yang YY, Hang HC, Pratt MR (2011) Chemical reporters for fluorescent detection and identification of O-GlcNAc-modified proteins reveal glycosylation of the ubiquitin ligase NEDD4-1. Proc Natl Acad Sci U S A 108:8146–8151.
  10. 10.
    Westcott NP, Hang HC (2014) Chemical reporters for exploring ADP-ribosylation and AMPylation at the host-pathogen interface. Curr Opin Chem Biol 23:56–62. Scholar
  11. 11.
    Grammel M, Luong P, Orth K, Hang HC (2011) A chemical reporter for protein AMPylation. J Am Chem Soc 133:17103–17105. Scholar
  12. 12.
    Yang YY, Ascano JM, Hang HC (2010) Bioorthogonal chemical reporters for monitoring protein acetylation. J Am Chem Soc 132:3640–3641. Scholar
  13. 13.
    Nagle JF, Tristram-Nagle S (2000) Structure of lipid bilayers. Biochim Biophys Acta 1469:159–195CrossRefGoogle Scholar
  14. 14.
    Marsh D (2001) Polarity and permeation profiles in lipid membranes. Proc Natl Acad Sci U S A 98:7777–7782. Scholar
  15. 15.
    Schultz C, Vajanaphanich M, Harootunian AT, Sammak PJ, Barrett KE, Tsien RY (1993) Acetoxymethyl esters of phosphates, enhancement of the permeability and potency of cAMP J Biol Chem 268:6316–6322Google Scholar
  16. 16.
    Schwede F, Brustugun OT, Zorn-Kruppa M, Doskeland SO, Jastorff B (2000) Membrane-permeant, bioactivatable analogues of cGMP as inducers of cell death in IPC-81 leukemia cells. Bioorg Med Chem Lett 10:571–573Google Scholar
  17. 17.
    Haedicke IE et al (2016) An enzyme-activatable and cell-permeable Mn(III)-porphyrin as a highly efficient T1 MRI contrast agent for cell labeling. Chem Sci 7:4308–4317.
  18. 18.
    Fritzsche S, Springer S (2014) Pulse-chase analysis for studying protein synthesis and maturation. Curr Protoc Protein Sci 78:30–33 (editorial board, John E Coligan [et al]).
  19. 19.
    Nishida Y et al (2015) SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol Cell 59:321–332.
  20. 20.
    Schuetz A et al (2007) Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. Structure 15:377–389.
  21. 21.
    Du Y et al (2015) Lysine malonylation is elevated in type 2 diabetic mouse models and enriched in metabolic associated proteins. Mol Cell Proteomics MCP 14:227–236.
  22. 22.
    Wagner GR, Payne RM (2013) Widespread and enzyme-independent Nepsilon-acetylation and Nepsilon-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J Biol Chem 288:29036–29045. Scholar
  23. 23.
    Colak G et al (2015) Proteomic and biochemical studies of lysine malonylation suggest its malonic aciduria-associated regulatory role in mitochondrial function and fatty acid oxidation. Mol Cell Proteomics MCP 14:3056–3071. Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of ChemistryThe University of Hong KongHong KongChina

Personalised recommendations