Role of the NH2-terminal domain of angiotensin II (ANG II) and [Sar1]angiotensin II on conformation and activity. NMR evidence for aromatic ring clustering and peptide backbone folding compared with [des-1,2,3]angiotensin II.
The role of the NH2 termini of angiotensin II (ANG II) and [Sar1]ANG II on conformation and activity were examined by proton NMR two-dimensional-J-correlated spectroscopy and one-dimensional nuclear Overhauser effect studies in the relatively nonpolar "receptor-simulating" environment provided by dimethyl sulfoxide-d6, using the biologically inactive COOH-terminal pentapeptide [des1,2,3]ANG II as control. Irradiation of C alpha H, C2H, and C4H proton resonances in ANG II and [Sar1]ANG II resulted in enhancements of Tyr and Phe ring proton resonances, indicating that the three aromatic rings cluster together. Very strong enhancements (17-22%) of the C alpha Y proton resonance in ANG II and [Sar1]ANG II upon irradiation of the C alpha H proton resonance, and vice versa, revealed that a Tyr-Ile-His bend is a predominant feature of the conformation of the two agonists. In contrast, saturation of the C alpha H and C alpha Y proton resonances in the control pentapeptide [des-1,2,3]ANG II did not produce, respectively, any C alpha Y or C alpha H proton nuclear Overhauser effect enhancement, illustrating the absence of a Tyr-Ile-His bend in the truncated ANG II peptide. The present findings indicate that the NH2-terminal domain of ANG II appears to have an essential role in generating the biologically active charge relay conformation of the hormone.
Matsoukas
J M
JM
Department of Chemistry, University of Patras, Greece.
Hondrelis
J
J
Keramida
M
M
Mavromoustakos
T
T
Makriyannis
A
A
Yamdagni
R
R
Wu
Q
Q
Moore
G J
GJ
D000465:Algorithms; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000737:chemistry*; D000809:Angiotensins / Q000737:chemistry*; D004121:Dimethyl Sulfoxide; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000809:Angiotensins; D010446:Peptide Fragments; D000804:Angiotensin II; C022782:angiotensin pentapeptide; C074793:angiotensin II, Sar(1)-; D004121:Dimethyl Sulfoxide