Open AccessHaloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
Author(s) -
Trent J. Oman,
Tania J. Lupoli,
TsungShing Andrew Wang,
Daniel Kahne,
Suzanne Walker,
Wilfred A. van der Donk
Publication year - 2011
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/ja206281k
Subject(s) - chemistry , lipid ii , peptidoglycan , efflux , peptide , biosynthesis , mutant , biochemistry , membrane , bacterial cell structure , substrate (aquarium) , stereochemistry , stoichiometry , bacteria , cell wall , enzyme , organic chemistry , gene , genetics , oceanography , biology , geology
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.
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