The solution structure of sarafotoxin-c. Implications for ligand recognition by endothelin receptors.
The solution structure of sarafotoxin-c has been determined using NMR spectroscopy. A total of 112 interproton distance constraints derived from two-dimensional NMR spectra were used to calculate a family of structures using a combination of distance geometry and dynamical simulated annealing calculations. The structures reveal a well defined alpha-helix extending from Glu9 to Cys15 and an N-terminal region (Cys1-Asp8) that is tightly constrained by disulfide bonds to Cys residues in the central helix. In contrast, the C-terminal region (His16-Trp21) does not adopt a defined conformation in the final family of structures. This is consistent with the paucity of NMR-derived structural constraints obtained for this region and leads to the suggestion that the C-terminal region oscillates rapidly between a number of substantially different conformers. It is proposed that differences between the central helix of the endothelin and sarafotoxin isopeptides might be important in binding of these ligands by the G protein-coupled endothelin receptors.
Mills
R G
RG
Department of Biochemistry, University of Sydney, New South Wales, Australia.
Ralston
G B
GB
King
G F
GF
D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012996:Solutions; D013057:Spectrum Analysis; D014461:Ultracentrifugation; D014757:Viper Venoms / Q000737:chemistry*
D010455:Peptides; D012996:Solutions; D014757:Viper Venoms; C089502:sarafotoxin-c