2. Academic Validation
  3. A small molecule inhibitor of fungal histone acetyltransferase Rtt109

A small molecule inhibitor of fungal histone acetyltransferase Rtt109

  • Bioorg Med Chem Lett. 2013 May 15;23(10):2853-9. doi: 10.1016/j.bmcl.2013.03.112.
Jessica Lopes da Rosa 1,  Vineeta Bajaj,  James Spoonamore,  Paul D Kaufman
Affiliations

Affiliation

  • 1 Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation St., LRB506, Worcester, MA 01605, USA.
PMID: 23587423 DOI: 10.1016/j.bmcl.2013.03.112
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.

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