1MJB

Crystal structure of yeast Esa1 histone acetyltransferase E338Q mutant complexed with acetyl coenzyme A

Summary for 1MJB

• Entry DOI: 10.2210/pdb1mjb/pdb
• Related: 1FY7 1MJ9 1MJA
• Descriptor: Esa1 protein, ACETYL COENZYME *A (3 entities in total)
• Functional Keywords: esa1, histone acetyltransferases, hat, myst, transferase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 34197.00

Authors

Yan, Y.,Harper, S.,Speicher, D.,Marmorstein, R. (deposition date: 2002-08-27, release date: 2002-10-30, Last modification date: 2024-10-30)

Primary citation

Yan, Y.,Harper, S.,Speicher, D.W.,Marmorstein, R.
The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate.
Nat.Struct.Biol., 9:862-869, 2002

PubMed 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.

PubMed: 12368900
DOI: 10.1038/nsb0902-638

Experimental method

X-RAY DIFFRACTION (2.5 Å)