Threonine6-bradykinin: Conformational study of a flexible peptide in dimethyl sulfoxide by NMR and ensemble calculations
✍ Scribed by Maria Pellegrini; Marina Gobbo; Raniero Rocchi; Evaristo Peggion; Stefano Mammi; Dale F. Mierke
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1996
- Tongue
- English
- Weight
- 905 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0006-3525
No coin nor oath required. For personal study only.
✦ Synopsis
The conformation of the natural peptide threonine6 ( Thr6) -bradykinin, Arg'-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 jact 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 Nterminal turn as a possible bioactive conformation.