The 3D structure in pure water of endothelin-1, a recently discovered potent vasoconstrictor peptide, has been determined at different pH and temperatures, using two-dimensional 1H NMR spectroscopy and constrained molecular dynamics (MD). 170 Inter- and intra-residue NOE interactions were quantified as volume integrals and translated into distances. All the coupling constants between the amidic and the α-protons have been measured and several dihedral angles, thus obtained, have been used as constraints for the MD. Some stereospecific assignments have also been performed. A family of eleven structures, satisfying the distance constraints to within 0.3 Å, was obtained and showed that the C-terminal, determinant for the binding with the receptor, has a well defined conformation. The correlation time measurements gave an average molecular volume consistent with monomeric species. The tertiary structure at neutral pH is that of a compact molecule, in which the C-terminal of the peptide folds back toward the α-helical segment (residues 9–16), in close proximity to the pro-R methyl group of Val12, as defined by important NOEs involving residues 17–21 and the α-helical core residues 9–14. The results are in agreement with the deuterium exchange experiments, which confirm the existence of a hydrophobic region also at the site of the C-terminal residues 19–21.
Tertiary structure of endothelin-1 in water by 1H NMR and molecular dynamics studies / E. Ragg, R. Mondelli, S. Penco, G. Bolis, L. Baumer, A. Guaragna. - In: JOURNAL OF THE CHEMICAL SOCIETY. PERKIN TRANSACTIONS 2. - ISSN 1472-779X. - :6(1994 Jun), pp. 1317-1326.
|Titolo:||Tertiary structure of endothelin-1 in water by 1H NMR and molecular dynamics studies|
RAGG, ENZIO MARIA (Primo)
MONDELLI, ROSANNA (Secondo)
|Parole Chiave:||endothelin-1 ; solution structure ; NMR ; Nuclear Overhauser Effect ; molecular dynamics|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||giu-1994|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1039/p29940001317|
|Appare nelle tipologie:||01 - Articolo su periodico|