A small molecule inhibitor of fungal histone acetyltransferase Rtt109.
The histone acetyltransferase Rtt109 is the sole enzyme responsible for acetylation of histone H3 lysine 56 (H3K56) in fungal organisms. Loss of Rtt109 renders fungal cells extremely sensitive to genotoxic agents, and prevents pathogenesis in several clinically important species. Here, via a high throughput chemical screen of >300,000 compounds, we ... discovered a chemical inhibitor of Rtt109 that does not inhibit other acetyltransferase enzymes. This compound inhibits Rtt109 regardless of which histone chaperone cofactor protein (Asf1 or Vps75) is present, and appears to inhibit Rtt109 via a tight-binding, uncompetitive mechanism.
Mesh Terms:
Dose-Response Relationship, Drug, Enzyme Inhibitors, Histone Acetyltransferases, Molecular Structure, Saccharomyces, Saccharomyces cerevisiae Proteins, Small Molecule Libraries, Structure-Activity Relationship
Dose-Response Relationship, Drug, Enzyme Inhibitors, Histone Acetyltransferases, Molecular Structure, Saccharomyces, Saccharomyces cerevisiae Proteins, Small Molecule Libraries, Structure-Activity Relationship
Bioorg. Med. Chem. Lett.
Date: May. 15, 2013
PubMed ID: 23587423
View in: Pubmed Google Scholar
Download Curated Data For This Publication
186095
Switch View:
- Interactions 7