title: Conformation of endothelin in aqueous ethylene glycol determined by 1H-NMR and molecular dynamics simulations.
abstract: 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.
authors.affiliation: Department of Macromolecular Modeling, Bristol-Myers Squibb Research Institute, Princeton, NJ 08543-4000.
authors.forename: S R
authors.initials: SR
authors.lastname: Krystek
authors.forename: D A
authors.initials: DA
authors.lastname: Bassolino
authors.forename: J
authors.initials: J
authors.lastname: Novotny
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: T M
authors.initials: TM
authors.lastname: Marschner
authors.forename: N H
authors.initials: NH
authors.lastname: Andersen
mesh_terms: 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
chemical_list: D016232:Endothelins; D005026:Ethylene Glycols; D006859:Hydrogen; D019855:Ethylene Glycol