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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetyltransferases / chemistry*
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Acetyltransferases / classification
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Acetyltransferases / genetics
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Acetyltransferases / metabolism*
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Amino Acid Sequence
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Binding Sites
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Catalysis
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Catalytic Domain
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Coenzyme A / chemistry
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Coenzyme A / metabolism*
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Conserved Sequence
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Crystallography, X-Ray
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Fungal Proteins / chemistry
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Fungal Proteins / classification
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Histone Acetyltransferases
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Histones / metabolism
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Models, Molecular
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Molecular Sequence Data
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Mutation / genetics
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Phenotype
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Protein Binding
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Protein Structure, Tertiary
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Structure-Activity Relationship
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Substrate Specificity
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Yeasts / enzymology*
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Yeasts / genetics
Substances
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Fungal Proteins
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Histones
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Saccharomyces cerevisiae Proteins
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Acetyltransferases
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Esa1 protein, S cerevisiae
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Histone Acetyltransferases
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Coenzyme A