Conformational analysis of [D-Ala9]alpha-factor and [L-Ala9]alpha-factor in solution and in the presence of lipid.
The conformations in solution and in the presence of lipid vesicles of [D-Ala9] and [L-Ala9] analogues of the alpha-factor (WHWLQLKPGQPMY) from the yeast Saccharomyces cerevisiae were examined by NMR spectroscopy. Although both peptides are flexible molecules, NOE and NH d delta/dT data indicate that the [D-Ala9]alpha-factor analogue in DMSO and aqueous solution adopts a type II beta-turn about residues 8 and 9. In contrast, various NMR parameters for the less active [L-Ala9] analogue do not provide evidence for a regular secondary structure in solution. Transfer NOE data indicate that for both peptides binding to the lipid is strongest for the N-terminal residues. The C-terminus of the [D-Ala9] analogue appears to be more constrained in the bound state than the C-terminus of the [L-Ala9] analogue. This result is consistent with transfer NOE evidence that the type II beta-turn conformation of the [D-Ala9]alpha-factor is maintained in the lipid bound state.
Gounarides
J S
JS
Department of Chemistry, Hunter College, City University of New York, New York 10021.
Broido
M S
MS
Becker
J M
JM
Naider
F R
FR
D000595:Amino Acid Sequence; D008055:Lipids / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D000072235:Mating Factor; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000187:drug effects; D010675:Pheromones / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D012995:Solubility; D013237:Stereoisomerism
D008055:Lipids; D008081:Liposomes; D010455:Peptides; D010675:Pheromones; D010713:Phosphatidylcholines; C079394:mating factor, Ala(9)-; D000072235:Mating Factor