DFT Study of the [Cu-Angiotensin II]~(2+) Complex Structure

摘要

Angiotensin II (Ang II, an octapeptide hormone: Aspl-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8) has been studied for several decades in investigations of the structure-dependent activity of the renin-angiotensin blood pressure regulation system. Metal ion influences on the biological activity of Ang II have also been investigated. Blood pressure was observed to increase as a result of the influence of Li, Na, Mg, and Ca ions on the renin-angiotensin system. Thus, it was proposed that the alkali (or alkaline-earth) metal ions induced conformational changes in Ang II that led to a conformational structure more suitable for the biological activity of Ang II. However, the Cu ion was observed to reduce blood pressure in a study performed by separate research group. A few different positive ion complexes [Cu-Ang II]~(n+) have been studied. The Cu binding sites of the [Cu-Ang II]~(1+) complex were suggested to have a Cu-NNNN geometry in the ATCUN (Amino Terminal Cu(II) and Ni(II)) complex. However, the Cu binding sites in the [Cu-Ang II]~(2+) complex were suggested to be the oxygen atoms of the carbonyl functional groups. The structure of Ang II has been reported to be S-shaped according to the results of an NMR experiment. This S-shaped structure has two potential metal ion binding pockets (Fig. 1).