A small molecule inhibitor of fungal histone acetyltransferase Rtt109
Program in Gene Function and Expression; Program in Molecular Medicine
Histone Acetyltransferases; Saccharomyces cerevisiae Proteins; Candida albicans
Biochemistry, Biophysics, and Structural Biology
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.
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Citation: Bioorg Med Chem Lett. 2013 May 15;23(10):2853-9. doi: 10.1016/j.bmcl.2013.03.112. Link to article on publisher's site
Bioorganic and medicinal chemistry letters
Lopes da Rosa Spiegler, Jessica; Bajaj, Vineeta; Spoonamore, James; and Kaufman, Paul D., "A small molecule inhibitor of fungal histone acetyltransferase Rtt109" (2013). University of Massachusetts Medical School Faculty Publications. 15.