The conformation of endothelin-1 in aqueous solution: NMR-derived constraints combined with distance geometry and molecular dynamics calculations.

The aqueous solution conformation of the bicyclic, 21 amino acid vasoconstrictor peptide, endothelin-1, has been determined using two dimensional NMR and a combination of distance geometry and molecular dynamics. The dominant structural feature is a helical region between Lys9 and Cys15 characterized by strong NHi-NHi+1 NOEs and several long range NOEs spanning 3 to 5 residues. Solvent inaccessibility and possible hydrogen bonding in the Cys3-Cys11 loop is suggested by the temperature independence of the chemical shifts of several amide protons. There is no evidence for association of the C-terminal hexapeptide with the bicyclic region.