The solution structure of human endothelin-2 a 1H-NMR and CD study

The solution structure of the vasoactive endogenous 21-amino-acid human endothelin-2 has been determined by NMR and CD techniques, in a mixed solvent of 100 mM aqueous acetic acid and 25% (by vol.) 1,1,1,3,3,3-hexafluoro-2-propanol. From NMR-derived restraints on upper limit distances and dihedral angles, distance geometry structures were calculated using the program DADAS90, and refined by simulated annealing in X-PLOR. The structure of endothelin-2 consists of an alpha-helix of residues 9 to 17, orientated anti-parallel to a short beta-strand of residues 1 to 3, linked together by a possible beta-turn type I of residues 5-8. These secondary structural elements are stabilised and positioned by two disulphide bonds between residues 1 and 15, and 3 and 11, respectively. The average root mean square deviation over residues 1-17 of 15 accepted low-energy conformers chosen to reflect the solution structure of endothelin-2, was 0.73 A for the backbone and 1.41 A for all heavy atoms. The data on endothelin-2 will be discussed and compared with what has been published on other endothelin/sarafotoxin peptides.