Conformation of endothelin in aqueous ethylene glycol determined by 1H-NMR and molecular dynamics simulations

• Published in: FEBS letters Vol. 281; no. 1; pp. 212 - 218
• Main Authors: Krystek, Stanley R., Bassolino, Donna A., Novotny, Jiri, Chen, Chinpan, Marschner, Thomas M., Andersen, Niels H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09.04.1991; Elsevier
• Subjects: Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Computer Simulation; Endothelin; Endothelins - chemistry; Ethylene Glycol; Ethylene Glycols; Fundamental and applied biological sciences. Psychology; Hydrogen; Magnetic Resonance Spectroscopy - methods; Mathematics; Models, Molecular; Molecular dynamics; NMR; Protein Conformation; Proteins; Three dimensional structure; Molecular dynamics; NMR; Endothelin; Three dimensional structure
• ISSN: 0014-5793; 1873-3468
• 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.