Conformation of deltorphin-I1 in membrane environment studied by two-dimensional NMR spectroscopy英文资料.pdfVIP

Eur. J. Biochem. 212, 185-191 (1993) 0FEBS 1993 Conformation of deltorphin-I1in membrane environment studied by two-dimensional NMR spectroscopy and molecular dynamics calculations Yasunori OHNO, Motozumi SEGAWA, Hirofumi OHISHI, Mitsunobu DOI, Kunihiro KITAMURA, Toshimasa ISHIDA, Masatoshi INOUE and Takashi IWASHITA Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Osaka, Japan Suntory Institute for Bioorganic Research, Osaka, Japan (Received October 22,1992)- EJB 921488 Two-dimensional homonuclear Hartmann-Hahn spectroscopy and NOESY (nuclear Overhauser effect and exchange spectroscopy) H-NMR techniques have been used to obtain complete proton resonance assignments and to perform a conformational investigation of deltorphin-I1 (Tyr-D-Ala- Phe-Glu-Val-Val-Gly-NH,), a naturally occurring selective opioid peptide, in the membrane-mi- metic micelles of perdeuterated dodecylphosphocholine. This was done in order to examine confor- mational characteristics that would be closely related to the selectivity towards the 8-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 10ps, which were energetically con- strained for the NOE interproton distances. Most of the possible conformers simulated showed a common feature such that the conformation of deltorphin-I1 is characterized by the S-shaped back- bone structure in which the turn conformation of the Val-Val-Gly-NH, sequence is located under the helically folded conformation of the N-terminal Tyr-D- Ala-Phe-Glu sequence. The possible relation-