TY - JOUR
T1 - Conformational study of [Met5]enkephalin-Arg-Phe in the presence of phosphatidylserine vesicles
AU - D'Alagni, Maria
AU - Delfini, Maurizio
AU - Di Nola, Alfredo
AU - Eisenberg, Moises
AU - Paci, Maurizio
AU - Roda, L. Giorgio
AU - Veglia, Gianluigi
PY - 1996
Y1 - 1996
N2 - The interaction of [Met5]enkephalin-Arg-Phe with phosphatidylserine (PtdSer) was studied by circular dichroism (CD), two-dimensional nuclear magnetic resonance spectroscopy, hybrid distance geometry simulated annealing (DG-SA) and molecular dynamics (MD) calculations. The very low solubility of [Met5]enkephalin-Arg-Phe and the instability of the solution containing PtdSer vesicles at low pH values did not allow us to observe the amide proton resonances in the usual two-dimensional NMR work. NOESY cross-peaks of protons of side chains from two-dimensional NMR were converted into distances which were used as restraints for modelling with DG-SA and MD. Our results indicate that, in aqueous solutions at pH 7.68 [Met5]enkephalin-Arg-Phe exists in the absence of PtdSer as a random distribution of conformers, whereas in the presence of PtdSer it adopts conformations containing a common orientation of the bonds of Cα2, Cα3, Cα4 and Cα5, although different orientations of the peptide planes are consistent with the results. Two of the reported conformers from MD simulations are characterized by the presence of a 2 ← 4 γ and inverse γ turns centered on Gly3. A gradual decline of order was observed when moving from the central moiety of the peptide to both the N-terminus and C-terminus. Finally, the DG-SA and MD calculations resulted in a structure such that the orientation of the Phe4 and Met5 side chains favours hydrophobic interactions with the apolar portion of the PtdSer vesicle to form a hydrophobic cluster. These data support the hypothesis of a role of lipids to modify the conformation of [Met5]enkephalin-Arg-Phe to permit the interactions with the receptor site.
AB - The interaction of [Met5]enkephalin-Arg-Phe with phosphatidylserine (PtdSer) was studied by circular dichroism (CD), two-dimensional nuclear magnetic resonance spectroscopy, hybrid distance geometry simulated annealing (DG-SA) and molecular dynamics (MD) calculations. The very low solubility of [Met5]enkephalin-Arg-Phe and the instability of the solution containing PtdSer vesicles at low pH values did not allow us to observe the amide proton resonances in the usual two-dimensional NMR work. NOESY cross-peaks of protons of side chains from two-dimensional NMR were converted into distances which were used as restraints for modelling with DG-SA and MD. Our results indicate that, in aqueous solutions at pH 7.68 [Met5]enkephalin-Arg-Phe exists in the absence of PtdSer as a random distribution of conformers, whereas in the presence of PtdSer it adopts conformations containing a common orientation of the bonds of Cα2, Cα3, Cα4 and Cα5, although different orientations of the peptide planes are consistent with the results. Two of the reported conformers from MD simulations are characterized by the presence of a 2 ← 4 γ and inverse γ turns centered on Gly3. A gradual decline of order was observed when moving from the central moiety of the peptide to both the N-terminus and C-terminus. Finally, the DG-SA and MD calculations resulted in a structure such that the orientation of the Phe4 and Met5 side chains favours hydrophobic interactions with the apolar portion of the PtdSer vesicle to form a hydrophobic cluster. These data support the hypothesis of a role of lipids to modify the conformation of [Met5]enkephalin-Arg-Phe to permit the interactions with the receptor site.
KW - Distance geometry
KW - Molecular dynamics calculation
KW - NMR
KW - Phosphatidylserine vesicle
KW - [Met5]enkephalin-Arg-Phe
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U2 - 10.1111/j.1432-1033.1996.0540h.x
DO - 10.1111/j.1432-1033.1996.0540h.x
M3 - Article
C2 - 8856052
AN - SCOPUS:0029759920
SN - 0014-2956
VL - 240
SP - 540
EP - 549
JO - European Journal of Biochemistry
JF - European Journal of Biochemistry
IS - 3
ER -