Specific Binding of Cinnamycin (Ro 09-0198) to Phosphatidylethanolamine. Comparison between Micellar and Membrane Environments

• Published in: Biochemistry (Easton) Vol. 42; no. 43; pp. 12570 - 12576
• Main Authors: Machaidze, Gia, Seelig, Joachim
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.11.2003
• Subjects: Bacteriocins; Calorimetry; Micelles; Peptides, Cyclic - metabolism; Phosphatidylethanolamines - metabolism; Thermodynamics
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi035225b

Cinnamycin (Ro 09-0198) is a tetracyclic peptide antibiotic that binds specifically to phosphatidylethanolamine (PE). Formation of a complex with phosphatidylethanolamine follows a 1:1 stoichiometry. Using high-sensitivity isothermal titration calorimetry (ITC), we have measured the thermodynamic parameters of complex formation for two different PE environments, namely, PE dissolved either in octyl glucoside (OG) micelles or in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer membrane. We have compared diacyl-PE with lyso-PE and have varied the carbon chain length from 6 to 18. Binding requires both a PE headgroup and at least one fatty acyl chain. The optimum chain length for complex formation (n) is eight. Longer chains do not enhance the binding affinity; for shorter chains, the interaction is weakened. The cinnamycin−PE complex has a binding constant K 0 of ∼107−108 M-1 in the POPC membrane and only ∼106 M-1 in the octyl glucoside micelle. The difference can be attributed to the nonspecific hydrophobic interaction of cinnamycin with the lipid membrane. Complex formation is enthalpy-driven in OG micelles, whereas enthalpy and entropy make equal contributions in bilayer membranes. However, for the optimum chain length (n) of eight, the binding reaction is also completely enthalpy-driven for the bilayer membrane.