N-lysine propionylation controls the activity of propionyl-CoA synthetase

J Biol Chem. 2007 Oct 12;282(41):30239-45. doi: 10.1074/jbc.M704409200. Epub 2007 Aug 7.


Reversible protein acetylation is a ubiquitous means for the rapid control of diverse cellular processes. Acetyltransferase enzymes transfer the acetyl group from acetyl-CoA to lysine residues, while deacetylase enzymes catalyze removal of the acetyl group by hydrolysis or by an NAD(+)-dependent reaction. Propionyl-coenzyme A (CoA), like acetyl-CoA, is a high energy product of fatty acid metabolism and is produced through a similar chemical reaction. Because acetyl-CoA is the donor molecule for protein acetylation, we investigated whether proteins can be propionylated in vivo, using propionyl-CoA as the donor molecule. We report that the Salmonella enterica propionyl-CoA synthetase enzyme PrpE is propionylated in vivo at lysine 592; propionylation inactivates PrpE. The propionyl-lysine modification is introduced by bacterial Gcn-5-related N-acetyltransferase enzymes and can be removed by bacterial and human Sir2 enzymes (sirtuins). Like the sirtuin deacetylation reaction, sirtuin-catalyzed depropionylation is NAD(+)-dependent and produces a byproduct, O-propionyl ADP-ribose, analogous to the O-acetyl ADP-ribose sirtuin product of deacetylation. Only a subset of the human sirtuins with deacetylase activity could also depropionylate substrate. The regulation of cellular propionyl-CoA by propionylation of PrpE parallels regulation of acetyl-CoA by acetylation of acetyl-CoA synthetase and raises the possibility that propionylation may serve as a regulatory modification in higher organisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Coenzyme A Ligases / chemistry*
  • Coenzyme A Ligases / metabolism
  • Humans
  • Lysine / chemistry*
  • Mitochondrial Proteins / chemistry
  • Molecular Conformation
  • NAD / chemistry
  • Nicotinamidase / metabolism
  • Peptides / chemistry
  • Salmonella enterica / enzymology*
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuin 3
  • Sirtuins / chemistry
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Time Factors


  • Mitochondrial Proteins
  • Peptides
  • NAD
  • SIRT1 protein, human
  • SIRT2 protein, human
  • SIRT3 protein, human
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuin 3
  • Sirtuins
  • Nicotinamidase
  • Coenzyme A Ligases
  • propionate - CoA ligase
  • Lysine