Residue Leu-641 of Acetyl-CoA Synthetase Is Critical for the Acetylation of Residue Lys-609 by the Protein Acetyltransferase Enzyme of Salmonella Enterica

J Biol Chem. 2005 Jul 15;280(28):26200-5. doi: 10.1074/jbc.M504863200. Epub 2005 May 17.

Abstract

Posttranslational regulation of protein function by acetylation is present throughout nature. Regulation of protein function by Sir2 protein (sirtuin) deacetylases is conserved in all domains of life. In the prokaryote Salmonella enterica, the metabolic enzyme acetyl-coenzyme A synthetase (Acs) is regulated by a Sir2-dependent protein acetylation/deacetylation system (SDPADS). The recent identification of the acetyltransferase enzyme responsible for the acetylation of Acs defined the SDPADS in prokaryotes. This report identifies one residue in Acs, Leu-641, which is critical for the acetylation of Acs by the protein acetyltransferase enzyme. In vivo and in vitro evidence shows that mutations at Leu-641 prevent the acetylation of Acs by protein acetyltransferase, maintain the Acs enzyme in its active state, and bypass the need for sirtuin deacetylase activity during growth on acetate.

Publication types

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

MeSH terms

  • Acetate-CoA Ligase / chemistry*
  • Acetates / chemistry
  • Acetates / pharmacology
  • Acetylation
  • Acetyltransferases / chemistry*
  • Acetyltransferases / metabolism
  • Alleles
  • Amino Acid Sequence
  • Arabinose / pharmacology
  • Cell Proliferation
  • Culture Media / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation, Bacterial*
  • Gene Expression Regulation, Enzymologic*
  • Genotype
  • Glutathione Transferase / metabolism
  • Humans
  • In Vitro Techniques
  • Leucine / chemistry*
  • Ligands
  • Models, Biological
  • Models, Chemical
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Salmonella enterica / enzymology*
  • Sequence Homology, Amino Acid
  • Sirtuins / metabolism
  • Substrate Specificity
  • Time Factors

Substances

  • Acetates
  • Culture Media
  • Ligands
  • Arabinose
  • Acetyltransferases
  • Glutathione Transferase
  • Sirtuins
  • Acetate-CoA Ligase
  • Leucine