Inhibition of Histone Lysine Acetyltransferases by Coenzyme A Analogs.

ABSTRACT: Histone lysine acetylation is a widespread posttranslational modification, essential for vital functions in eukaryotic organisms. Histone lysine acetyltransferases (KATs) employ acetyl-coenzyme A as a universal acetyl donor for acetylation of lysine residues in histone and non-histone proteins. Despite the biomedicinal importance of modulation of the KAT activity, application of the acetyl-coenzyme A cosubstrate structure for the design of potent and selective inhibitors has been underexplored. Here, we developed functionalized coenzyme A analogs as inhibitors against human histone lysine acetyltransferases GCN5, KAT8, and HAT1. In contrast to the unmodified coenzyme A, which was found to be a poor inhibitor of GCN5 and KAT8 (IC₅₀ > 150 μM), we showed that a ketone-substituted c

SUBMITTER: Voukia F 

PROVIDER: S-EPMC12899889 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature