Krystek S R, Bassolino D A, Novotny J, Chen C, Marschner T M, Andersen N H
Department of Macromolecular Modeling, Bristol-Myers Squibb Research Institute, Princeton, NJ 08543-4000.
FEBS Lett. 1991 Apr 9;281(1-2):212-8. doi: 10.1016/0014-5793(91)80396-k.
The solution conformation of a 21-residue vasoconstrictor peptide endothelin-1 (ET-1) in water-ethylene glycol has been determined by two-dimensional 1H-NMR spectroscopy and constrained molecular dynamics simulations. The N-terminus (residues 1-4) appears to undergo conformational averaging and no single structure consistent with the NMR constraints could be found for this region. Residues 5-8 form a turn, and residues 9-16 exist in a helical conformation. A flexible 'hinge' between residues 8-9 allows various orientations of the turn relative to the helix. Another 'hinge' at residue 17 connects the extended C-terminus to the bicyclic core region (residues 1-15). Residues important for binding and biological activity form a contiguous surface on one side of the helix, with the two disulfides extending from the other side of the helix.
