Conformational analysis of met‐enkephalin in both aqueous solution and in the presence of sodium dodecyl sulfate micelles using multidimensional NMR and molecular modeling

Proton and 13C chemical shift assignments are reported for the neuropeptide Met‐enkephalin (ME) in both aqueous solution and in the presence of 50 mM sodium dodecyl sulfate (SDS). Rotating frame nuclear Overhauser enhancement spectroscopy was used to qualitatively describe interproton distances. These distances were then used as restraints in the distance geometry based molecular modeling program Dspace, developed by Hare Research to generate sets of conformations of ME. The resulting aqueous solution conformations of ME were determined to exhibit characteristic of an extended random‐coil polypeptide with no distinguishable secondary structure. The resulting set of solution conformations of ME in the presence of 50 m M SDS exhibited characteristics of an amphiphilic type IV β turn that are stabilized by hydrophobic aromatic‐aromatic interactions between the side chains of Tyr1 and Phe4. © 1992 John Wiley & Sons, Inc.

[1]  V. Hruby,et al.  Binding and Information Transfer in Conformationally Restricted Peptides , 1986 .

[2]  J. K. Young,et al.  The interactions of neuropeptides with membrane model systems: A case study , 1992, Biopolymers.

[3]  V. Garsky,et al.  Proton magnetic resonance studies of conformation and flexibility of enkephalin peptides , 1976, Nature.

[4]  C. Deber,et al.  Transfer of peptide hormones from aqueous to membrane phases , 1985 .

[5]  H. Scheraga,et al.  Chain reversals in proteins. , 1973, Biochimica et biophysica acta.

[6]  M. Summers,et al.  High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach. , 1990, Biochemistry.

[7]  B. Montgomery Pettitt,et al.  The conformational properties of the delta opioid peptide [D-Pen2,D-Pen5]enkephalin in aqueous solution determined by NMR and energy minimization calculations , 1988 .

[8]  H. Morris,et al.  Identification of two related pentapeptides from the brain with potent opiate agonist activity , 1975, Nature.

[9]  K Wüthrich,et al.  Sequential resonance assignments in protein 1H nuclear magnetic resonance spectra. Computation of sterically allowed proton-proton distances and statistical analysis of proton-proton distances in single crystal protein conformations. , 1982, Journal of molecular biology.

[10]  D. G. Davis,et al.  Practical aspects of two-dimensional transverse NOE spectroscopy , 1985 .

[11]  L. Zetta,et al.  270-MHz 1H nuclear-magnetic-resonance study of met-enkephalin in solvent mixtures. Conformational transition from dimethylsulphoxide to water. , 1982, European journal of biochemistry.

[12]  W. Mattice,et al.  Circular dichroism and absorption study of the structure of methionine-enkephalin in solution. , 1978, Biochemical and biophysical research communications.

[13]  V. Hruby,et al.  [D-Pen2, L-Cys5]enkephalinamide and[D-Pen2, D-Cys5] enkephalinamide, conformationally constrained cyclic enkephalinamide analogs with delta receptor specificity. , 1982, Biochemical and biophysical research communications.

[14]  A. Fischman,et al.  Conformational studies on [Pro3, Gly4]-oxytocin in dimethyl sulfoxide by 1H nuclear magnetic resonance spectroscopy: evidence for a type II beta turn in the cyclic moiety. , 1978, Biochemistry.

[15]  A. K. Lala,et al.  Conformation of Met5-enkephalin determined by high field PMR spectroscopy , 1976, Nature.

[16]  G A Petsko,et al.  Aromatic-aromatic interaction: a mechanism of protein structure stabilization. , 1985, Science.

[17]  Horst Kessler,et al.  Conformation and Biological Activity of Cyclic Peptides , 1982 .

[18]  A. De Marco,et al.  Evidence for a folded structure of met‐enkephalin in membrane mimetic systems: 1H‐nmr studies in sodiumdodecylsulfate, lyso‐phosphatidylcholine, and mixed lyso‐phosphatidylcholine/sulfatide micelles , 1986, Biopolymers.

[19]  R. Bradley,et al.  Conformational states of enkephalins in solution. , 1977, Biochemical and biophysical research communications.

[20]  R. Griffey,et al.  Correlation of proton and nitrogen-15 chemical shifts by multiple quantum NMR☆ , 1983 .

[21]  Fluorescence study on the conformation of a cyclic enkephalin analog in aqueous solution. , 1983, Biochemical and biophysical research communications.

[22]  R. Deslauriers,et al.  Interaction of opioid peptides with model membranes. A carbon-13 nuclear magnetic study of enkephalin binding to phosphatidylserine. , 1980, Biochemistry.

[23]  C. Deber,et al.  Evidence for a folded conformation of methionine- and leucine-enkephalin in a membrane environment. , 1984, The Journal of biological chemistry.

[24]  Ad Bax,et al.  MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy , 1985 .

[25]  A. Bax,et al.  1H and13C Assignments from Sensitivity-Enhanced Detection of Heteronuclear Multiple-Bond Connectivity by 2D Multiple Quantum NMR , 1986 .

[26]  L. Gierasch,et al.  Nuclear magnetic resonance analysis and conformational characterization of a cyclic decapeptide antagonist of gonadotropin-releasing hormone. , 1987, Biochemistry.

[27]  J. Griffin,et al.  Conformation of [Leu5]enkephalin from X-ray diffraction: features important for recognition at opiate receptor. , 1978, Science.

[28]  J. Hughes,et al.  Some thoughts on the significance of enkephalin, the endogenous ligand. , 1975, Life sciences.