CONFORMATION OF RENIN SUBSTRATE (ANGIOTENSINOGEN) IN WATER IS DIFFERENT FROM DMSO - A H-1-NMR AND MOLECULAR-DYNAMICS STUDY

The conformation of angiotensinogen, a tetradecapeptide, with the sequ ence rg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8-His9-Leu10-Leu11 -Val12-Tyr13-S er14, was studied in aqueous medium by 2D NMR spectroscopy. Complete r esonance assignments were made using a combination of DQF-COSY, TOCSY and NOESY spectra. The kinetics of deuterium exchange of NH protons we re 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 characteri zed by a beta-turn around the tetrapeptide sequence Val3-Tyr4-Ile5-His 6, two gamma-bends at Tyr4 and Leu10 and a sharp turn around Val12. Th e conformation of angiotensinogen in water is radically different from the conformation in DMSO reported earlier.