1.C.90 The Carnocyclin A (Carnocyclin) Family

Carnocyclin A (CclA) is a 60-amino acid circular bacteriocin produced by Carnobacterium maltaromaticum UAL307. It exhibits potent activity against many Gram-positive bacteria. Lipid bilayer and single channel recording techniques were applied to study the molecular mechanisms by which CclA interacts with the lipid membrane and exerts its antimicrobial effects. Gong et al. 2009 showed that CclA can form ion channels with a conductance of 35 pS in a 150 mM NaCl solution. Channel activity displays a linear current-voltage relationship, is anion-selective, and its activation is strongly voltage-dependent. The formation of ion channels by CclA is driven by the presence of a negative membrane potential and may result in dissipation of the membrane potential.

An amide bond links the N and C termini of this bacteriocin, imparting stability and structural integrity to this peptide. Several other circular bacteriocins have been reported, yet only one (enterocin AS-48) has been structurally characterized. Martin-Visscher et al. (2008;2009) have determined the solution structure of CclA by NMR and further examined its anion binding and membrane channel properties. The results revealed that CclA preferentially binds halide anions and has a structure that is surprisingly similar to that of AS-48 despite low sequence identity, a different oligomeric state, and disparate function. CclA folds into a compact globular bundle, comprised of four helices surrounding a hydrophobic core. NMR studies show two fluoride ion binding modes for CclA. Although other circular bacteriocins are likely to have diverse mechanisms of action, many may have a common structural motif. This shared three-dimensional arrangement resembles the fold of mammalian saposins, peptides that either directly lyse membranes or serve as activators of lipid-degrading enzymes (Martin-Visscher et al., 2009).

The reaction catalized by Carnocyclin A is:

Ions (in) → Ions (out)

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