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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1mj9

E.C. namehistone acetyltransferase
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz) 2.3.1.48
CSA Homologues of 1mj91fy7,2giv,2ou2,2ozu,2pq8,2rc4,
CSA Entries With UniProtID Q08649
CSA Entries With EC Number 2.3.1.48
PDBe Entry 1mj9
PDBSum Entry 1mj9
MACiE Entry 1mj9

Literature Report

IntroductionESA1 Histone acyl transferase is able to catalyse the acylation of histone proteins at specific lysine residues, using acetyl coA as the acyl donor for the reaction. Acylation of histone proteins is important in the regulatation of DNA transcription, as it causes the chromasones to condense and become inaccessible to the enzymes required for unwinding and unzipping the DNA. As a result study of the mechanism by which acylation occurs is of interest to geneticists, and opens the possibility of manipulation of gene expression by designing activators or inhibitors of the enzymes catalysing the process. Histone acyl transferases in eukaryotes show much sequence homology, and can consequently be assigned to a superfamily (HAT). However, the mechanism of reaction is not the same; many work with direct attack from the target lysine residue on the acetyl-COA but the MYST subfamily, of which ESA1 is a representative, have an acylated enzyme intermediate in the reaction mechanism.
MechansimThe reaction mechanism obeys ping-pong kinetics, with initial nucleophilic attack from Cys 304 on the acetyl coA assisted by deprotonation of Cys 304 by the general base Glu 338. This results in the transfer of the acyl moiety to Cys 304. The target lysine, deprotonated by Glu 338 then acts as a nucleophile, attacking the acyl moiety and resulting in Cys 304 acting as a leaving group. This transfers the acyl moiety to the Lysines epsilon NH group and forms the final product.
Reaction

Catalytic Sites for 1mj9

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA338338macie:sideChainActs as general acid base first in the deprotonation of Cys 304 to allow it to act as a nucleophile, then in the deprotonation of the target lysine to allow it to act as a nucleophile.
SerA304304macie:sideChainActs as nucleophile to covalently attach to the acyl group of acetyl coA. Then acts as leaving group to allow transfer of the acyl group to the target lysine residue.

Literature References

Notes:
Yan Y
The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate.
Nat Struct Biol 2002 9 862-869
PubMed: 12368900
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