Conformation of renin substrate (angiotensinogen) in water is different from DMSO: a1H NMR and molecular dynamics study

Abstract

The conformation of angiotensinogen, a tetradecapeptide, with the sequence Asp1–Arg2–Val3–Tyr4–Ile5–His6–Pro7–Phe8–His9–Leu10–Leu11–Val12–Tyr13–Ser14, was studied in aqueous medium by 2D NMR spectroscopy. Complete resonance assignments were made using a combination of DQF-COSY, TOCSY and NOESY spectra. The kinetics of deuterium exchange of NH protons were also studied. The NMR results indicate the presence of at least two conformations in dynamic equilibrium. A total of 39 NOEs were used in the restrained molecular dynamics simulation to generate the solution structure. The dominant conformation of angiotensinogen is characterized by a β-turn around the tetrapeptide sequence Val3–Tyr4–Ile5–His6, two γ-bends at Tyr4 and Leu10 and a sharp turn around Val12. The conformation of angiotensinogen in water is radically different from the conformation in DMSO reported earlier. ©1998 John Wiley & Sons, Ltd.