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. 2002 Nov;9(11):862-9.
doi: 10.1038/nsb849.

The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate

Yuan Yan  1 , Sandy Harper, David W Speicher, Ronen Marmorstein
Affiliations

The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate

Yuan Yan et al. Nat Struct Biol. 2002 Nov.

Abstract

Yeast ESA1 is a member of the MYST subfamily of histone acetyltransferases (HATs), which use acetyl-coenzyme A (CoA) to acetylate specific Lys residues within histones to regulate gene expression. The structure of an ESA1-CoA complex reveals structural similarity to the catalytic core of the GCN5/PCAF subfamily of HAT proteins. Here we report additional structural and functional studies on ESA1 that demonstrate that histone acetylation proceeds through an acetyl-cysteine enzyme intermediate. This Cys residue is strictly conserved within the MYST members, suggesting a common mode of catalysis by this HAT subfamily. However, this mode of catalysis differs dramatically from the GCN5/PCAF subfamily, which mediate direct nucleophilic attack of the acetyl-CoA cofactor by the enzyme-deprotonated substrate lysine of the histone. These results demonstrate that different HAT subfamilies can use distinct catalytic mechanisms, which have implications for their distinct biological roles and for the development of HAT-specific inhibitors.

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Comment in

  • Methyl magic and HAT tricks.
    Dutnall RN, Denu JM. Dutnall RN, et al. Nat Struct Biol. 2002 Dec;9(12):888-91. doi: 10.1038/nsb1202-888. Nat Struct Biol. 2002. PMID: 12447351 No abstract available.

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