Conformations of synthetic tetradecapeptide renin substrate and of angiotensin I in aqueous solution.
The properties of aqueous solutions of synthetic renin substrate tetradecapeptide (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser) were examined through electrometric titrations, infrared and circular dichroism spectroscopy, and spectrofluorometry. Titration studies of angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) were also made, whose results indicated a flexible folded conformation similar to that previously proposed for the octapeptide angiotensin II, with a possible additional beta turn at the C terminus. The experimental results of the tetradecapeptide study, associated with Chou and Fasman calculations and with an analysis of structure-activity relationships in renin substrates and competitive inhibitors, led to the proposal of a beta turn involving the His-Pro-Phe-His sequence of the tetradecapeptide. This beta turn would be stabilized by beta-antiparallel interaction between residues 3-4 and 10-12 and by electrostatic attraction between the N-terminal ammonium and C-terminal carboxylate groups and would be destabilized below pH 5 by electrostatic repulsion between His6 and His9. The capacity to assume this conformation is related to structural requirements for renin substrates and competitive inhibitors.
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000031:analogs & derivatives; D000808:Angiotensinogen; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D012083:Renin / Q000378:metabolism; D012995:Solubility; D013055:Spectrophotometry, Infrared
D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin