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Plasmid DNA Preparation> | … The gene encoding HsAcAS (cytoplasmic) gene (Genebank AF263614.1) containing an N-terminal His tag and TEV site was synthesized by GenScript and cloned into pCDNA 3.1 vector, using Nhe1 and Xho1 restriction sites. The plasmid was transformed into XL1 cells then a … | Get A Quote |
We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds. In vitro biochemical assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 direct... More