Fig. 1.
Effect of acyclic nucleotide phosphonates (ANPs) on the enzymatic activity of anthrax EF and host adenylyl cyclase. (A) The chemical structure of adefovir dipivoxil (bis-POM-PMEA). (B) Chemical structures of four ANPs and their Ki values for EF and CyaA. (C) Lineweaver-Burk plot for the inhibition of EF by PMEApp. (D) Inhibition of EF and three mammalian adenylyl cyclase isoforms, bovine type I (mACI), rat type II (mACII), and mouse type V (mACV), by PMEApp. Adenylyl cyclase assays were performed with 17 pM EF3, 1 μM CaM, and 1 μM free Ca2+ (B and C) and with 20 μg of Sf9 cell membrane, 0.5 μM Gsα, 100 μM forskolin, 30 μM AlF3, 5 mM MgCl2, and 10 mM NaF (D). Mean ± SE is representative of at least two experiments, and the representative data for B are shown in Figs. 5 and 6, which are published as supporting information on the PNAS web site.