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A small molecule inhibitor of fungal histone acetyltransferase Rtt109.

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.

SUBMITTER: Lopes da Rosa J

PROVIDER: S-EPMC3654155 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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A small molecule inhibitor of fungal histone acetyltransferase Rtt109.

Lopes da Rosa Jessica J Bajaj Vineeta V Spoonamore James J Kaufman Paul D PD

Bioorganic & medicinal chemistry letters 20130404 10

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 hi ...[more]

PMID: 23587423

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