Nmr and molecular modeling investigations of the neuropeptide bradykinin in three different solvent systems: DMSO, 9:1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles.
The linear nonapeptide hormone bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) is involved, either directly or indirectly, in a wide variety of physiological processes, particularly pain and hyperanalgesia. Additional evidence suggests that bradykinin also plays a major role in inflammatory response, asthma, sepsis, and symptoms associated with the rhinoviral infection. It has long been speculated that a beta-turn at the C-terminus of bradykinin plays a major role in the biological activity of the neuropeptide. The beta-turn forming potential of bradykinin in three vastly different local chemical environments, DMSO, 9:1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles, was investigated using two-dimensional homonuclear nmr experiments coupled with simulated annealing calculations. The results of these investigations show that in all three systems residues 6-9 of the C-terminus adopt very similar beta-turn like structures. These results suggest that the beta-turn at the C-terminus of bradykinin is an important secondary structural feature for receptor recognition and binding.
Young
J K
JK
Department of Chemistry, Mississippi State University, Mississippi 39762.
Hicks
R P
RP
D000595:Amino Acid Sequence; D001920:Bradykinin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012997:Solvents
D012997:Solvents; D001920:Bradykinin