Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases

Mol Cell. 2000 Nov;6(5):1195-205. doi: 10.1016/s1097-2765(00)00116-7.

Abstract

Esa1 is the catalytic subunit of the NuA4 histone acetylase (HAT) complex that acetylates histone H4, and it is a member of the MYST family of HAT proteins that includes the MOZ oncoprotein and the HIV-1 Tat interacting protein Tip60. Here we report the X-ray crystal structure of the HAT domain of Esa1 bound to coenzyme A and investigate the protein's catalytic mechanism. Our data reveal that Esa1 contains a central core domain harboring a putative catalytic base, and flanking domains that are implicated in histone binding. Comparisons with the Gcn5/PCAF and Hat1 proteins suggest a unified mechanism of catalysis and histone binding by HAT proteins, whereby a structurally conserved core domain mediates catalysis, and sequence variability within a structurally related N- and C-terminal scaffold determines substrate specificity.

Publication types

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

MeSH terms

  • Acetyltransferases / chemistry*
  • Acetyltransferases / classification
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Catalytic Domain
  • Coenzyme A / chemistry
  • Coenzyme A / metabolism*
  • Conserved Sequence
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Fungal Proteins / classification
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Histone Acetyltransferases
  • Histones / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Phenotype
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Structure-Activity Relationship
  • Substrate Specificity
  • Yeasts / enzymology*
  • Yeasts / genetics

Substances

  • Fungal Proteins
  • Histones
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • Esa1 protein, S cerevisiae
  • Histone Acetyltransferases
  • Coenzyme A

Associated data

  • PDB/1FY7