Molecular characterization of an rsmD-like rRNA methyltransferase from the Wolbachia endosymbiont of Brugia malayi and antifilarial activity of specific inhibitors of the enzyme.

ABSTRACT: The endosymbiotic organism Wolbachia is an attractive antifilarial drug target. Here we report on the cloning and expression of an rsmD-like rRNA methyltransferase from the Wolbachia endosymbiont of Brugia malayi, its molecular properties, and assays for specific inhibitors. The gene was found to be expressed in all the major life stages of B. malayi. The purified enzyme expressed in Escherichia coli was found to be in monomer form in its native state. The activities of the specific inhibitors (heteroaryl compounds) against the enzyme were tested with B. malayi adult and microfilariae for 7 days in vitro at various concentrations, and NSC-659390 proved to be the most potent compound (50% inhibitory concentration [IC50], 0.32 μM), followed by NSC-658343 (IC50, 4.13 μM) and NSC-657589 (IC50,

SUBMITTER: Rana AK 

PROVIDER: S-EPMC3719755 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature