Biochemical characterization and discovery of inhibitors for <i>Pf</i>Sir2A: new tricks for an old enzyme.

ABSTRACT: The Sir2 enzyme from Plasmodium falciparum (PfSir2A) is essential for the antigenic variation of this parasite, and its inhibition is expected to have therapeutic effects for malaria. Selective PfSir2A inhibitors are not available yet, partially due to the fact that this enzyme demonstrates extremely weak in vitro deacetylase activity, making the characterization of its inhibitors rather challenging. In the current study, we report the biochemical characterization and inhibitor discovery for this enzyme. PfSir2A exhibits greater enzymatic activity in the presence of DNA for both the peptide and histone protein substrates, suggesting that nucleosomes may be the real substrates of this enzyme. Indeed, it demonstrates robust deacetylase activity against nucl

SUBMITTER: Donu D 

PROVIDER: S-EPMC11784564 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature