Structural characterization of lipopeptide agonists for the bradykinin B2 receptor

✍ Scribed by Craig Giragossian; Elena Nardi; Caroline Savery; Maria Pellegrini; Stefania Meini; Carlo A. Maggi; Anna Maria Papini; Dale F. Mierke

• Publisher: Wiley (John Wiley & Sons)
• Year: 2001
• Tongue: English
• Weight: 147 KB
• Volume: 58
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/1097-0282(20010415)58:5<511::aid-bip1026>3.0.co;2-z

✦ Synopsis

Lys analogues of bradykinin, have been determined by highresolution NMR in a zwitterionic lipoid environment. Radical-induced relaxation of the 1 H NMR signals was used to probe the topological orientation of the peptides with respect to the zwitterionic lipid interface. The radical-induced relaxation and molecular dynamics (MD) data indicated that the palmitic acid and N-terminal amino acid residues embed into the micelles, while the rest of the polypeptide chain is closely associated with the water-micelle interface. Throughout the entire nuclear Overhauser effect restrained MD simulation, a nonideal type I ␤-turn was observed in the C-terminus of PKD between residues 6 and 9, and a ␥-turn was observed in the C-terminus of PGKD between residues 6 and 7. Therefore, the additional glycine has a dramatic effect on the structural preferences of the biologically important C-terminus, an effect brought about by the interaction with the lipid environment. These structural features are correlated to the biological activity at the bradykinin B2 receptor.