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J Am Chem Soc. 2011 Nov 9;133(44):17544-7. doi: 10.1021/ja206281k. Epub 2011 Oct 17.

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

Author information

1
Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.

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 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 findings, the data support a model in which a 1:2:2 lipid II:Halα:Halβ complex inhibits cell wall biosynthesis and mediates pore formation, resulting in loss of membrane potential and potassium efflux.

PMID:
22003874
PMCID:
PMC3206492
DOI:
10.1021/ja206281k
[Indexed for MEDLINE]
Free PMC Article

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