Haloduracin 伪 Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry

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• 作者：Trent J. Oman ; Tania J. Lupoli ; Tsung-Shing Andrew Wang ; Daniel Kahne ; Suzanne Walker ; Wilfred A. van der Donk
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：November 9, 2011
• 年：2011
• 卷：133
• 期：44
• 页码：17544-17547
• 全文大小：790K
• 年卷期：v.133,no.44(November 9, 2011)
• ISSN：1520-5126

文摘

The two-peptide lantibiotic haloduracin is composed of two post-translationally modified polycyclic peptides that synergistically act on Gram-positive bacteria. We show here that Hal伪 inhibits the transglycosylation reaction catalyzed by PBP1b by binding in a 2:1 stoichiometry to its substrate lipid II. Hal尾 and the mutant Hal伪-E22Q were not able to inhibit this step in peptidoglycan biosynthesis, but Hal伪 with its leader peptide still attached was a potent inhibitor. Combined with previous findings, the data support a model in which a 1:2:2 lipid II:Hal伪:Hal尾 complex inhibits cell wall biosynthesis and mediates pore formation, resulting in loss of membrane potential and potassium efflux.