Conformation of endothelin in aqueous ethylene glycol determined by 1H-NMR and molecular dynamics simulations.
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.
Krystek
S R
SR
Department of Macromolecular Modeling, Bristol-Myers Squibb Research Institute, Princeton, NJ 08543-4000.
Bassolino
D A
DA
Novotny
J
J
Chen
C
C
Marschner
T M
TM
Andersen
N H
NH
D003198:Computer Simulation; D016232:Endothelins / Q000737:chemistry*; D019855:Ethylene Glycol; D005026:Ethylene Glycols; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008433:Mathematics; D008958:Models, Molecular; D011487:Protein Conformation
D016232:Endothelins; D005026:Ethylene Glycols; D006859:Hydrogen; D019855:Ethylene Glycol