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

Trent J. Oman, Tania Lupoli, Tsung Shing Andrew Wang, Daniel Kahne, Suzanne Walker, Wilfred A. Van Der Donk

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)17544-17547
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number44
DOIs
StatePublished - Nov 9 2011

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Biosynthesis
Stoichiometry
Lipids
Peptides
Bacteriocins
Peptidoglycan
Gram-Positive Bacteria
Protein Sorting Signals
Membrane Potentials
Cell Wall
Potassium
Bacteria
Cells
Membranes
Substrates
muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Haloduracin α binds the peptidoglycan precursor lipid II with 2:1 stoichiometry. / Oman, Trent J.; Lupoli, Tania; Wang, Tsung Shing Andrew; Kahne, Daniel; Walker, Suzanne; Van Der Donk, Wilfred A.

In: Journal of the American Chemical Society, Vol. 133, No. 44, 09.11.2011, p. 17544-17547.

Research output: Contribution to journalArticle

Oman, Trent J. ; Lupoli, Tania ; Wang, Tsung Shing Andrew ; Kahne, Daniel ; Walker, Suzanne ; Van Der Donk, Wilfred A. / Haloduracin α binds the peptidoglycan precursor lipid II with 2:1 stoichiometry. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 44. pp. 17544-17547.
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