1n9v
Differences and Similarities in Solution Structures of Angiotensin I & II: Implication for Structure-Function Relationship.Differences and Similarities in Solution Structures of Angiotensin I & II: Implication for Structure-Function Relationship.
Structural highlights
DiseaseANGT_HUMAN Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:145500. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause. Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:267430. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).[1] FunctionANGT_HUMAN Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.[2] [3] [4] Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.[5] [6] [7] Angiotensin-3: stimulates aldosterone release.[8] [9] [10] Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).[11] [12] [13] Publication Abstract from PubMedConformational analysis of angiotensin I (AI) and II (AII) peptides has been performed through 2D 1H-NMR spectroscopy in dimethylsulfoxide and 2,2,2-trifluoroethanol/H2O. The solution structural models of AI and AII have been determined in dimethylsulfoxide using NOE distance and 3JHNHalpha coupling constants. Finally, the AI family of models resulting from restrained energy minimization (REM) refinement, exhibits pairwise rmsd values for the family ensemble 0.26 +/- 0.13 A, 1.05 +/- 0.23 A, for backbone and heavy atoms, respectively, and the distance penalty function is calculated at 0.075 +/- 0.006 A2. Comparable results have been afforded for AII ensemble (rmsd values 0.30 +/- 0.22 A, 1.38 +/- 0.48 A for backbone and heavy atoms, respectively; distance penalty function is 0.029 +/- 0.003 A2). The two peptides demonstrate similar N-terminal and different C-terminal conformation as a consequence of the presence/absence of the His9-Leu10 dipeptide, which plays an important role in the different biological function of the two peptides. Other conformational variations focused on the side-chain orientation of aromatic residues, which constitute a biologically relevant hydrophobic core and whose inter-residue contacts are strong in dimethylsulfoxide and are retained even in mixed organic-aqueous media. Detailed analysis of the peptide structural features attempts to elucidate the conformational role of the C-terminal dipeptide to the different binding affinity of AI and AII towards the AT1 receptor and sets the basis for understanding the factors that might govern free- or bound-depended AII structural differentiation. Comparison of the solution structures of angiotensin I & II. Implication for structure-function relationship.,Spyroulias GA, Nikolakopoulou P, Tzakos A, Gerothanassis IP, Magafa V, Manessi-Zoupa E, Cordopatis P Eur J Biochem. 2003 May;270(10):2163-73. PMID:12752436[14] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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