Abstract
A conformation of the neurohypophyseal hormone oxytocin in solution is proposed. The structure possesses, in addition to the β-turn comprised of the sequence -L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl- in the ring component of the hormonal molecule, a second β-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 β-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 β-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 β-turn by forming a hydrogen bond with the N-H of the leucine residue, which is part of the end peptide of the second β-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.
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