Allosteric Regulation of a Protein Acetyltransferase in Micromonospora aurantiaca by the Amino Acids Cysteine and Arginine*

Background: Reversible lysine acetylation of proteins is ubiquitous in actinomycetales. Results: Arginine and cysteine allosterically regulate the protein lysine acetyltransferase Micau_1670 in Micromonospora aurantiaca. Conclusion: The amino acid-binding domain is fused to GCN5-related acetyltransferases, conferring amino acid-induced allosteric regulation to these enzymes. Significance: Activities mediated by amino acids in these acetyltransferases directly link amino acid metabolism to cellular acetylation of proteins. ACT domains (amino acid-binding domains) are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Seventy proteins with ACT-GCN5-related N-acetyltransferase (GNAT) domain organization were found in actinomycetales. In this study, we investigate the ACT-containing GNAT acetyltransferase, Micau_1670 (MaKat), from Micromonospora aurantiaca ATCC 27029. Arginine and cysteine were identified as ligands by monitoring the conformational changes that occur upon amino acids binding to the ACT domain in the MaKat protein using FRET assay. It was found that MaKat is an amino acid-regulated protein acetyltransferase, whereas arginine and cysteine stimulated the activity of MaKat with regard to acetylation of acetyl-CoA synthetase (Micau_0428). Our research reveals the biochemical characterization of a protein acetyltransferase that contains a fusion of a GNAT domain with an ACT domain and provides a novel signaling pathway for regulating cellular protein acetylation. These findings indicate that acetylation of proteins and acetyltransferase activity may be tightly linked to cellular concentrations of some amino acids in actinomycetales.

• Publication year

  2014

• Venue

  Journal of Biological Chemistry

• Publication date

  2014-08-14

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M114.579078PMID 25124041PMCID PMC4175341
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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