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Haloduracin ? binds the peptidoglycan precursor lipid II with 2:1 stoichiometry.

ABSTRACT: 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? inhibits the transglycosylation reaction catalyzed by PBP1b by binding in a 2:1 stoichiometry to its substrate lipid II. Hal? and the mutant Hal?-E22Q were not able to inhibit this step in peptidoglycan biosynthesis, but Hal? 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?:Hal? complex inhibits cell wall biosynthesis and mediates pore formation, resulting in loss of membrane potential and potassium efflux.

SUBMITTER: Oman TJ

PROVIDER: S-EPMC3206492 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Haloduracin α binds the peptidoglycan precursor lipid II with 2:1 stoichiometry.

Oman Trent J TJ Lupoli Tania J TJ Wang Tsung-Shing Andrew TS Kahne Daniel D Walker Suzanne S van der Donk Wilfred A WA

Journal of the American Chemical Society 20111017 44

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 Halα inhibits the transglycosylation reaction catalyzed by PBP1b by binding in a 2:1 stoichiometry to its substrate lipid II. Halβ and the mutant Halα-E22Q were not able to inhibit this step in peptidoglycan biosynthesis, but Halα with its leader peptide still attached was a potent inhibitor. Combined with previous find ...[more]

PMID: 22003874

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