Structure and properties of the metastable bacteriocin Lcn972 from Lactococcus lactis

Lactococcus lactis subsp. lactis IPLA 972 produces a polypeptide bacteriocin of 7.5 kDa which has a bactericidal effect on sensitive lactococci, inhibiting septum formation in dividing cells. The active form is a monomer that is metastable under normal conditions but is stabilised by glycerol. The NMR structure of Lcn972 shows a β-sandwich comprising two three-stranded antiparallel β-sheets. Detaching the final strand could allow the sandwich to open, and the irreversible unfolding leads to a loss of antibacterial activity. Covalent linkage of the final strand should increase the stability of Lcn972 and facilitate the study of its interaction with lipid II.

► Lcn972 is a peptide antibiotic with heat sensitive activity. ► The NMR structure is a compact beta sandwich. ► The structure could easily unfold by fraying from the C-terminus. ► Cross-linking might produce a more stable antibiotic.