Structural characterization of lipopeptide agonists for the bradykinin B2 receptor

Citation
C. Giragossian et al., Structural characterization of lipopeptide agonists for the bradykinin B2 receptor, BIOPOLYMERS, 58(5), 2001, pp. 511-520
Citations number
34
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOPOLYMERS
ISSN journal
00063525 → ACNP
Volume
58
Issue
5
Year of publication
2001
Pages
511 - 520
Database
ISI
SICI code
0006-3525(20010415)58:5<511:SCOLAF>2.0.ZU;2-5
Abstract
The conformational features of Pam-Lys(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5 )-Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PKD) and Pam-Gly(-1)-Lys(0)-Arg(1)-Pro(2) -Pro(3)-Gly(4)-Phe(5-)Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PGKD), the Pam-Lys an d Pam-Gly-Lys analogues of bradykinin have been determined by high-resoluti on NMR in a zwitterionic lipoid environment. Radical-induced relaxation of the H-1 NMR signals was used to probe the topological orientation of the pe ptides with respect to the zwitterionic lipid interface. The radical-induce d relaxation and molecular dynamics (MD) data indicated that the palmitic a cid and N-terminal amino acid residues embed into the micelles, while the r est of the polypeptide chain is closely associated with the water-micelle i nterface. Throughout the entire nuclear Overhauser effect restrained MD sim ulation, a nonideal type I beta -turn was observed in the C-terminus of PKD between residues 6 and 9, and a gamma -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 envi ronment. These structural features are correlated to the biological activit y at the bradykinin B2 receptor. (C) 2001 John Wiley & Sons, Inc.