A comparison of the conformation of sucrose octasulfate, free and bound to acidic fibroblast growth factor.

The conformation of sucrose octasulfate free in solution has been determined based on high-resolution NMR spectroscopy. Three-bond 1H-1H scalar coupling constants, laboratory and rotating frame NOEs, long-range 1H-13C scalar coupling constants, and chemical-shift temperature and ionic-strength dependence were used, aided by molecular mechanics calculations. By modification of a pulse sequence designed for measuring long-range 1H-13C coupling constants, it was possible to obtain an accurate value for the 3JC2f-H1g despite the confounding presence of 3JHH of similar value. Free sucrose octasulfate appears to assume a conformation significantly different from any of the eight conformations observed bound to acidic fibroblast growth factor, as determined in a previous X-ray crystallographic study [X. Zhu, B.T. Hsu, and D.C. Rees, Structure, 1 (1993) 27-34]. Strong electrostatic interactions between guest and host may be the dominant factor in deformation of sucrose octasulfate. The implications of this study for protein-carbohydrate interactions and the effects of the presence of sulfate groups on the flexibility of sucrose are also discussed.