title: Quantum mechanical calculations useful for determining the mechanism of action of fosfomycin.
abstract: CNDO/2 calculations were performed to determine at the molecular level the mechanism of action of the antibiotic fosfomycin, (--)-(1R,2S)-(1,2-epoxypropyl)phosphonic acid. Fosfomycin, a bacterial cell wall inhibitor, is known to act as a competitive inhibitor of N-acetylglucosamine-3-O-enolpyruvyl transferase, the normal substrate of which is phosphoenolpyruvate. Both compounds were studied, and the theoretical calculations revealed that the preferred conformations of phosphoenolpyruvate and fosfomycin presented the same spatial charge distributions on the active sites, the values of which are in complete agreement with the experimental observations. These results permit the projection of some details of the receptor, with implications for the modification of fosfomycin to increase its antibiotic activity.
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005578:Fosfomycin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D010728:Phosphoenolpyruvate / Q000494:pharmacology; D011789:Quantum Theory
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D010728:Phosphoenolpyruvate