Conformation of renin substrate (angiotensinogen) in water is different from DMSO: a 1H NMR and molecular dynamics study
✍ Scribed by Anant B. Patel; Sudha Srivastava; Ratna S. Phadke; Evans Coutinho; Shantaram Kamath
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 386 KB
- Volume
- 36
- Category
- Article
- ISSN
- 0749-1581
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✦ Synopsis
The conformation of angiotensinogen, a tetradecapeptide, with the sequence Asp1ÈArg2ÈVal3ÈTyr4È Ile5ÈHis6ÈPro7ÈPhe8ÈHis9ÈLeu10ÈLeu11ÈVal12ÈTyr13ÈSer14, 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 b-turn around the tetrapeptide sequence Val3ÈTyr4ÈIle5ÈHis6, two c-bends at Tyr4 and Leu10 and a sharp turn around Val12. The conformation of angiotensinogen in water is radically di †erent from the conformation in DMSO reported earlier.