ISSN:
0006-3525
Keywords:
bradykinin
;
nmr
;
peptide conformation
;
ensemble averages
;
distance geometry calculations
;
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The conformation of the natural peptide threonine6 (Thr6)-bradykinin, Arg1-Pro2-Pro3-Gly4-Phe5-Thr6-Pro7-Phe8-Arg9, was investigated in DMSO by nmr spectroscopy and computer simulations. The structural analysis of the Thr6-peptide is made particularly interesting by the fact that despite the high sequence homology with native bradykinin (only one conservative substitution: Ser6/Thr6) there is a marked and significant difference in the biological profiles of the two peptides.The nmr spectra indicate a relatively flexible structure with the presence of an N-terminal turn. Standard distance geometry calculations failed to produce structures in accord with the experimental observations; the resulting structures are indeed too rigid and conformationally restricted for the nmr data. The results of ensemble calculations reveal conformational changes occurring rapidly on the nmr time scale and allow for the establishment of a series of disordered conformations, prevalently extended with a partially populated turn in residues 2-5, which when considered together, as an average, fulfill the experimental restraints. The structural characterization of (Thr6)-bradykinin supports the hypothesis of the significant role of the residue at position 6 on both conformation as well as biological activities and suggests a N-terminal turn as a possible bioactive conformation. © 1997 John Wiley & Sons, Inc. Biopoly 40: 561-569, 1996
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
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