Solution structure of the catalytic domain of GCN5 histone acetyltransferase bound to coenzyme A

Nature. 1999 Jul 1;400(6739):86-9. doi: 10.1038/21922.


Gene transcription requires the release of inactive DNA from its packaging of histone proteins. Following the discovery of the first transcription-associated histone acetyltransferase, tetrahymena GCN5, it was shown that yeast GCN5 is recruited to the promoter and causes hyper-acetylation of histones and transcriptional activation of target genes, establishing a direct connection between histone acetylation and transcriptional activation. Many other important transcription regulators have been found to have histone acetyltransferase activity, including TAFII230/250, p300/CBP and its associated factor PCAF. Here we present the solution structure of the catalytic domain of tGCN5 (residues 47-210) in complex with coenzyme A. The structure contains two domains; the amino-terminal domain is similar to those of other GCN5-related N-acetyltransferases but the carboxy-terminal domain is not. Coenzyme A binds in a deep hydrophobic pocket between the two domains. Chemical shift changes upon titration with histone H3 peptides indicate a binding site at the domain boundary opposite to the coenzyme A site. The structural data indicate a single-step acetyl-transfer reaction mechanism catalysed by a hydrogen bond to the backbone amide group of leucine 126 and the side-chain carboxyl group of a conserved acidic residue.

Publication types

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

MeSH terms

  • Acetyltransferases / chemistry*
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Alanine / genetics
  • Amino Acid Sequence
  • Catalysis
  • Catalytic Domain
  • Coenzyme A / chemistry*
  • Coenzyme A / metabolism
  • Histone Acetyltransferases
  • Histones / metabolism
  • Lysine / metabolism
  • Macromolecular Substances
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Point Mutation
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Saccharomyces cerevisiae Proteins*
  • Solutions


  • Histones
  • Macromolecular Substances
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Solutions
  • Acetyltransferases
  • Histone Acetyltransferases
  • tGCN5 histone acetyltransferase
  • Lysine
  • Alanine
  • Coenzyme A

Associated data

  • PDB/5GCN