acetyltransferases

Acetyltransferases are enzymes that catalyze the transfer of an acetyl group from acetyl-CoA to a target molecule. Acceptors include proteins, nucleic acids, small molecules, sugars, and antibiotics. The reaction produces CoA and an acetylated substrate, and acetylation can alter activity, stability, localization, or interactions of the substrate.

The field includes protein acetyltransferases, which modify lysine or N-terminal residues, and small-molecule acetyltransferases that modify metabolites or drugs. Structurally, many acetyltransferases share a conserved acetyltransferase fold, with the GNAT family being the most widespread, alongside other folds such as the MYST family for histone substrates.

Histone acetyltransferases, such as GCN5/PCAF and the p300/CBP family, acetylate lysines on histones to promote transcription. N-terminal acetyltransferases (NATs), including NatA–NatE, act co-translationally on nascent polypeptides, contributing to protein stability and trafficking.

Small-molecule acetyltransferases include aminoglycoside acetyltransferases, which inactivate aminoglycoside antibiotics and contribute to resistance. Other enzymes, such as arylalkylamine N-acetyltransferases, participate in metabolic processes such as melatonin synthesis. The range of substrates highlights functional diversity among acetyltransferases.

Mechanistically, acetyltransferases often position acetyl-CoA and the substrate to enable nucleophilic attack on the acetyl carbon. They are regulated by gene expression and post-translational modifications, and interact with deacetylases to establish dynamic acetylation states that influence cellular processes.