Does the solid-state structure of endothelin-1 provide insights concerning the solution-state conformational equilibrium?
Additional NMR data (local NOE ratios and chemical shifts) for endothelin-1 supporting the existence of a relatively regular helix initiated abruptly at Lys9 (with Asp8 as an N-cap) and extending in all cases to Cys15 (and in a frayed form to Asp18 in some analogs) is presented. The recent solids-state structure [Janes et al. (1994), Nature Struct. Biol. 1, 311-319], in contrast, places the helix in the extreme C-terminal section of structure and the Lys9-Tyr13 segment is not helical. The X-ray structure does not predict the NOEs or chemical shifts observed for endothelins in aqueous media containing polar organic co-solvents. An analysis of the chemical shift data for reporter groups indicates that the helical conformational preference of endothelins is not significantly altered by the addition of acetonitrile, acetic acid, or ethylene glycol. The validity of the analytic strategy is supported by results for both more rigid and less helical analogs. We conclude that the structure observed in crystals obtained from purely aqueous media is influenced by intermolecular interactions in the solid state and is not a significant contributor to the conformational equilibrium observed for monomeric ET-1.
Lee
G M
GM
Department of Chemistry, University of Washington, Seattle 98195.
Chen
C
C
Marschner
T M
TM
Andersen
N H
NH
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D016232:Endothelins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions
D016232:Endothelins; D012996:Solutions