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- W2034708368 abstract "Abstract The pressor and myotropic activities in vivo of the linear octapeptide hormone Angiotensin-II (A-II) (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) are enchanced by divalent metal ions. In model membrane systems consisting of phospholipid vesicles, A-II behaves as ionophore in translocating Mn(II) ions across the bilayer [1] with a rate constant which is pH dependent with an apparent pK of 7.7. Since A-II is itself interacting with the bilayer in pH dependent way [2], the metal-A-II coordination modes are expected to play a central role in the biological effect of the hormone. In this report nuclear and electron relaxation features of the A-IIMn(II) complexes in aqueous solution are measured with the aim of delineating the metal binding sites. The ESR intensity loss and the appearance of ‘slow motion’ features in the X-band ESR spectrum of Mn(II) were taken to demonstrate a main binding interaction with one (or two) carboxyl groups, since the ESR parameters were pH independent over the whole range investigated (pH = 4–8). The paramagnetic contribution to nuclear relaxation rates. T −1 ip , were measured for aromatic protons of A-II: (a typical spectrum is shown in Fig. 1) and, since T −1 2p −1 1p for all the protons, i) fast exchange conditions were assumed and ii) dipolar only contributions to T −1 1p were considered. The T −1 1p and T −1 2p values were therefore taken to demonstrate that the imidazole moiety of His 6 is a secondary metal binding site. The pH dependence of T −1 1p , reported in Table I, clearly showed that the binding to His 6 is relevant in a narrow pH range only, which could be explained in t001 . I:pH dependence of T −1 1p for Phe and His H 2 protons of A-II. [A-II] = 0.01 M ; [Mn ++ ] = 0.01 m M ; T = 295 K. pH T 1p −1 (sec −1 Phe His H 2 4.5 0.12 0.14 5.5 0.18 0.62 6.0 0.22 1.83 6.5 0.24 6.22 7.0 0.22 4.90 7.5 0.19 2.05 8.0 0.14 1.62 terms of intramolecular structuring within the peptide molecule opposing metal coordination driven by deprotonation of the imidazole ring." @default.
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- W2034708368 date "1983-01-01" @default.
- W2034708368 modified "2023-09-27" @default.
- W2034708368 title "The role of divalent metal ions in the mechanism of action of the hormone angiotensin-II" @default.
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- W2034708368 doi "https://doi.org/10.1016/s0020-1693(00)95345-3" @default.
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