Conformation of deltorphin-II in membrane environment studied by two-dimensional NMR spectroscopy and molecular dynamics calculations.
Two-dimensional homonuclear Hartmann-Hahn spectroscopy and NOESY (nuclear Overhauser effect and exchange spectroscopy) 1H-NMR techniques have been used to obtain complete proton resonance assignments and to perform a conformational investigation of deltorphin-II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), a naturally occurring delta-selective opioid peptide, in the membrane-mimetic micelles of perdeuterated dodecylphosphocholine. This was done in order to examine conformational characteristics that would be closely related to the selectivity towards the delta-opioid receptor. With the use of the proton-proton distances derived from NOESY measurements, 50 possible three-dimensional structures were generated by means of distance-geometry calculations, and 25 of them were subjected to the molecular-dynamics simulations of 10 ps, which were energetically constrained for the NOE interproton distances. Most of the possible conformers simulated showed a common feature such that the conformation of deltorphin-II is characterized by the S-shaped back-bone structure in which the turn conformation of the Val-Val-Gly-NH2 sequence is located under the helically folded conformation of the N-terminal Tyr-D-Ala-Phe-Glu sequence. The possible relationship between this conformational characteristic and the delta-opioid-receptor selectivity has been discussed.
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Y
Y
Ohno
M
M
Segawa
H
H
Ohishi
M
M
Doi
K
K
Kitamura
T
T
Ishida
M
M
Inoue
T
T
Iwashita
D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013696:Temperature
D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C060209:deltorphin II, Ala(2)-