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Replacement of Phe 8 in substance P by Tyr (Tyr 8 ‐SP) alters the conformation of the peptide in DMSO, water, and lipid bilayers
Author(s) -
Patel Anant B.,
Srivastava Sudha,
Coutinho Evans,
Phadke Ratna S.
Publication year - 1999
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(199911)50:6<602::aid-bip5>3.0.co;2-n
Subject(s) - chemistry , random coil , peptide , stereochemistry , phosphatidylcholine , biophysics , crystallography , circular dichroism , membrane , biochemistry , phospholipid , biology
The conformation of [Tyr 8 ]SP (Y8SP) in dimethylsulfoxide (DMSO), water, and dipalmitoyl phosphatidylcholine (DPPC) bilayers has been investigated by two‐dimensional nmr and molecular dynamics simulations. Molecular modeling of the conformation of Y8SP by incorporating nuclear Overhauser effects as distance restraints shows wide differences in its conformation in the three media. In DMSO, the main structural features are γ‐bends along with a nonspecific bend around Gln 6 –Phe 7 –Tyr 8 . The random coil structure seen in water is transformed into a β‐turn around the segment Gln 5 –Gln 6 –Phe 7 –Tyr 8 when Y8SP is incorporated into DPPC bilayers. The lower biological activity of Y8SP compared to the native peptide (SP) has been attributed to the absence of any helix like structure at the central residues, a feature shown to be an important prerequisite for SP and SP agonists to bind to the neurokinin 1 tachykinin receptor. © 1999 John Wiley & Sons, Inc. Biopoly 50: 602–612, 1999