The conformational features of Pam–Lys0–Arg1–Pro2–Pro3–Gly4–Phe5–Ser6–Pro7–Phe8– Arg9–OH (PKD) and Pam–Gly21–Lys0–Arg1–Pro2–Pro3–Gly4–Phe5–Ser6–Pro7–Phe8–Arg9–OH (PGKD), the Pam–Lys and Pam–Gly–Lys analogues of bradykinin, have been determined by highresolution NMR in a zwitterionic lipoid environment. Radical-induced relaxation of the 1HNMR 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 b-turn was observed in the C-terminus of PKD between residues 6 and 9, and a g-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.
Structural Characterization of Lipopeptide Agonists for the Bradykinin B2 Receptor / GIRAGOSSIAN C.; NARDI E.; SAVERY C.; PELLEGRINI M.; MEINI S.; MAGGI C.A.; A.M. PAPINI; MIERKE D.. - In: BIOPOLYMERS. - ISSN 0006-3525. - STAMPA. - 58:(2001), pp. 511-520.
Structural Characterization of Lipopeptide Agonists for the Bradykinin B2 Receptor.
PAPINI, ANNA MARIA;
2001
Abstract
The conformational features of Pam–Lys0–Arg1–Pro2–Pro3–Gly4–Phe5–Ser6–Pro7–Phe8– Arg9–OH (PKD) and Pam–Gly21–Lys0–Arg1–Pro2–Pro3–Gly4–Phe5–Ser6–Pro7–Phe8–Arg9–OH (PGKD), the Pam–Lys and Pam–Gly–Lys analogues of bradykinin, have been determined by highresolution NMR in a zwitterionic lipoid environment. Radical-induced relaxation of the 1HNMR 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 b-turn was observed in the C-terminus of PKD between residues 6 and 9, and a g-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.File | Dimensione | Formato | |
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