TY - JOUR
T1 - Structure-Activity Relationship Studies of the Two-Component Lantibiotic Haloduracin
AU - Cooper, Lisa E.
AU - McClerren, Amanda L.
AU - Chary, Anita
AU - van der Donk, Wilfred A.
N1 - This work was supported by the National Institutes of Health Grant GM58822. L.E.C. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award 5 T32 GM070421 from the National Institute of General Medical Sciences.
PY - 2008/10/20
Y1 - 2008/10/20
N2 - The lantibiotic haloduracin consists of two posttranslationally processed peptides, Halα and Halβ, which act in synergy to provide bactericidal activity. An in vitro haloduracin production system was used to examine the biological impact of disrupting individual thioether rings in each peptide. Surprisingly, the Halα B ring, which contains a highly conserved CTLTXEC motif, was expendable. This motif has been proposed to interact with haloduracin's predicted target, lipid II. Exchange of the glutamate residue in this motif for alanine or glutamine completely abolished antibacterial activity. This study also established that Halα-Ser26 and Halβ-Ser22 escape dehydration, requiring revision of the Halβ structure previously proposed. Extracellular proteases secreted by the producer strain can remove the leader peptide, and the Halα cystine that is dispensable for bioactivity protects Halα from further proteolytic degradation.
AB - The lantibiotic haloduracin consists of two posttranslationally processed peptides, Halα and Halβ, which act in synergy to provide bactericidal activity. An in vitro haloduracin production system was used to examine the biological impact of disrupting individual thioether rings in each peptide. Surprisingly, the Halα B ring, which contains a highly conserved CTLTXEC motif, was expendable. This motif has been proposed to interact with haloduracin's predicted target, lipid II. Exchange of the glutamate residue in this motif for alanine or glutamine completely abolished antibacterial activity. This study also established that Halα-Ser26 and Halβ-Ser22 escape dehydration, requiring revision of the Halβ structure previously proposed. Extracellular proteases secreted by the producer strain can remove the leader peptide, and the Halα cystine that is dispensable for bioactivity protects Halα from further proteolytic degradation.
KW - CHEMBIO
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U2 - 10.1016/j.chembiol.2008.07.020
DO - 10.1016/j.chembiol.2008.07.020
M3 - Article
C2 - 18940665
AN - SCOPUS:53649090841
SN - 1074-5521
VL - 15
SP - 1035
EP - 1045
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 10
ER -