Mechanism of Action of Bacitracin: Complexation with Metal Ion and C 55 -Isoprenyl Pyrophosphate

作者：K. J. Stone, Jack L. Strominger · 发表于：Proceedings of the National Academy of Sciences · 年份：1971 · DOI：10.1073/pnas.68.12.3223 · 被引用次数：378 · 研究领域：Chromatography in Natural Products、Cancer Treatment and Pharmacology、Plant-based Medicinal Research

The inhibition by bacitracin of the enzymatic dephosphorylation of C(55)-isoprenyl pyrophosphate is abolished by the addition of chelating agents. If, however, the chelating agent is added after a preincubation of bacitracin with a divalent cation and the lipid substrate, then its addition has little effect, indicating that bacitracin, metal ion, and C(55)-isoprenyl pyrophosphate form a complex. Various divalent cations can participate in complex formation, but monovalent cations are ineffective. A direct demonstration of the formation of a complex between the C(55)-isoprenyl pyrophosphate and bacitracin in the presence of metal ions was obtained. Molecular models that show one possible conformation for a complex between bacitracin and the C(55)-isoprenyl pyrophosphate, in which the metal ion acts as a bridge between the two compounds, are presented.