Three-dimensional structure of a type VI turn in a linear peptide in water solution. Evidence for stacking of aromatic rings as a major stabilizing factor.

Structures have been calculated for the folded conformation found at high population in the cis isomeric form of the peptide NH3(+)-Ser-Tyr-Pro-Phe-Asp-Val-COO- (SYPFDV) in aqueous solution, using distance geometry and restrained molecular dynamics. A number of NMR parameters, including NOE distance restraints and phi and chi 1 dihedral angle restraints derived from coupling constants were used in the calculation. The restraints were carefully selected to exclude those that might have a significant contribution from the unfolded states of the peptide, so that the calculated structure represents only the folded form (present at about 70% population) and contains no information on the other members of the conformational ensemble. The calculations give a tight family of structures in the region Tyr2 to Phe4, all containing a type VI turn with an unusual disposition of the aromatic rings of Tyr and Phe, which stack against the proline ring. Both backbone and side-chain conformations are well defined in this region. At the ends of the molecule the polypeptide chain is disordered. The structures are consistent with all of the available NMR information, including upfield chemical shifts observed for the proline ring protons in the cis isomer, and with the independently determined proline ring pucker. There is no evidence for cross-turn hydrogen bonding. According to the calculated structures, the major source of stabilization of the turn conformation appears to be the stacking of the aromatic and proline rings.