NMR investigation of cyclo7,10[C7,X9,C10,Nle12] analogues of the alpha-factor from Saccharomyces cerevisiae

• Published in: Biopolymers Vol. 34; no. 6; p. 709
• Main Authors: Gounarides, J S, Xue, C B, Becker, J M, Naider, F
• Format: Journal Article
• Language: English
• Published: United States 01-06-1994
• Subjects: Amino Acid Sequence; Fungal Proteins - chemistry; Magnetic Resonance Spectroscopy - methods; Mating Factor; Molecular Sequence Data; Peptides - chemistry; Peptides, Cyclic - chemistry; Pheromones - chemistry; Protein Conformation; Protein Structure, Secondary; Saccharomyces cerevisiae; Solutions
• ISSN: 0006-3525
• DOI: 10.1002/bip.360340604

The cyclo7,10[Cys7,Cys10,Nle12], cyclo7,10[Cys7,D-Ala9,Cys10,Nle12], and cyclo7,10[Cys7,L-Ala9,Cys10,Nle12] analogues of the alpha-factor mating pheromone (WHWLQLKPGQPMY) of the yeast Saccharomyces cerevisiae were studied in DMSO/water (80:20) and aqueous solution by nmr spectroscopy. In addition, the cyclo7,10[Cys7,D-Val9,Cys10,Nle12]alpha-fa ctor was examined in DMSO/water. Nuclear Overhauser effect (NOE) and NH d delta/dT data indicate that the cyclo7,10[Cys7,D-Val9,Cys10,Nle12]alpha-fa ctor adopts a type II beta-turn in DMSO/water and that the cyclo7,10[Cys7,D-Ala9,Cys10,Nle12]- and cyclo7,10[Cys7,L-Ala9,Cys10,Nle12]alpha-fa ctor analogues adopt type II and type I/III beta-turns, respectively, in both DMSO/water and aqueous solutions. In aqueous solution, residues 8 and 9 of the cyclo7,10[Cys7,Nle12] alpha-factor appear to adopt at least two distinct conformations, one of these being identified as a type I/III beta-turn. In contrast, the cyclo7,10[Cys7,Cys10,Nle12] alpha-factor appears to adopt predominately a type II beta-turn in DMSO/water. Quantitative NOE measurements of the cyclo7,10[Cys7,Cys10,Nle12]-, cyclo7,10[Cys7,D-Val9,Cys10,Nle12]-, and cyclo7,10[Cys7,L-Ala9,Cys10,Nle12] alpha-factors in DMSO/water were used to derive three-dimensional structures of the cyclo7,10[Cys7,Pro8,X9,Cys10] portion of these analogues.