Comparison of the solution structures of angiotensin I & II - Implication for structure-function relationship

Conformational analysis of angiotensin I (AI) and II (AII) peptides has been performed through 2D (1) H-NMR spectroscopy in dimethylsulfoxide and 2,2,2-trifluoroethanol/H-2 O. The solution structural models of AI and AII have been determined in dimethylsulfoxide using NOE distance and (3) J (HNHalpha) coupling constants. Finally, the AI family of models resulting from restrained energy minimization (REM) refinement, exhibits pairwise rmsd values for the family ensemble 0.26 +/- 0.13 Angstrom, 1.05 +/- 0.23 Angstrom, for backbone and heavy atoms, respectively, and the distance penalty function is calculated at 0.075 +/- 0.006 Angstrom(2) . Comparable results have been afforded for AII ensemble (rmsd values 0.30 +/- 0.22 Angstrom, 1.38 +/- 0.48 Angstrom for backbone and heavy atoms, respectively; distance penalty function is 0.029 +/- 0.003 Angstrom(2) ). The two peptides demonstrate similar N-terminal and different C-terminal conformation as a consequence of the presence/absence of the His9-Leu10 dipeptide, which plays an important role in the different biological function of the two peptides. Other conformational variations focused on the side-chain orientation of aromatic residues, which constitute a biologically relevant hydrophobic core and whose inter-residue contacts are strong in dimethylsulfoxide and are retained even in mixed organic-aqueous media. Detailed analysis of the peptide structural features attempts to elucidate the conformational role of the C-terminal dipeptide to the different binding affinity of AI and AII towards the AT(1) receptor and sets the basis for understanding the factors that might govern free- or bound-depended AII structural differentiation.