Proposed Conformation of Oxytocin in Solution

Publisher Website
Google Scholar
Abstract
A conformation of the neurohypophyseal hormone oxytocin in solution is proposed. The structure possesses, in addition to the beta-turn comprised of the sequence -L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl- in the ring component of the hormonal molecule, a second beta-turn involving the C-terminal oxytocin sequence, -L-cysteinyl-L-prolyl-L-leucylglycinamide. The resulting oxytocin structure places the bulky side chains of the leucine and isoleucine residues, as well as the cyclic moiety of the proline residue, at corners of the two beta-turns. A critical role is played by the asparagine residue: its peptide N-H participates in the formation of the hydrogen-bonded cyclic structure of the beta-turn in the ring component of oxytocin and its peptide C=O can be hydrogen-bonded to the N-H of tyrosine, while its side chain C=O stabilizes the second beta-turn by forming a hydrogen bond with the N-H of the leucine residue, which is part of the end peptide of the second beta-turn. This conformational assignment of oxytocin is consistent with hydrogen-deuterium exchange studies, with plots of temperature dependence of peptide proton chemical shifts, and with the coupling constants for the NH-CH dihedral angles.