University of Massachusetts Medical School Faculty Publications

Title

A small molecule inhibitor of fungal histone acetyltransferase Rtt109

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Publication Date

5-15-2013

Document Type

Article

Subjects

Histone Acetyltransferases; Saccharomyces cerevisiae Proteins; Candida albicans

Disciplines

Biochemistry, Biophysics, and Structural Biology

Abstract

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.

Rights and Permissions

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

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Bioorganic and medicinal chemistry letters

PubMed ID

23587423