Structure-Activity Relationship Studies of the Two-Component Lantibiotic Haloduracin

Lisa E. Cooper, Amanda L. McClerren, Anita Chary, Wilfred A. van der Donk

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1035-1045
Number of pages11
JournalChemistry and Biology
Issue number10
StatePublished - Oct 20 2008



ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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