SOLUTION CONFORMATION OF AN ATRIAL NATRIURETIC PEPTIDE VARIANT SELECTIVE FOR THE TYPE-A RECEPTOR
[ANF_HUMAN] Defects in NPPA are the cause of familial atrial fibrillation type 6 (ATFB6) [MIM:612201]. Atrial fibrillation is a common disorder of cardiac rhythm that is hereditary in a small subgroup of patients. It is characterized by disorganized atrial electrical activity, progressive deterioration of atrial electromechanical function and ineffective pumping of blood into the ventricles. It can be associated with palpitations, syncope, thromboembolic stroke, and congestive heart failure.
[ANF_HUMAN] Hormone playing a key role in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. Also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus. Specifically binds and stimulates the cGMP production of the NPR1 receptor. Binds the clearance receptor NPR3.
Publication Abstract from PubMed
Two-dimensional NMR spectroscopy has been used to characterize the solution conformation of an atrial natriuretic peptide (ANP) variant which is selective for the human natriuretic peptide receptor A (NPR-A) relative to receptor C (NPR-C). The ANP mutant, containing six substitutions, has reduced flexibility in aqueous solution relative to wild-type ANP and allows the observation of sufficient NOE connectivities for structure determination by distance geometry and restrained molecular dynamics calculations. The solution conformation is reasonably well defined, having an average backbone atom rms deviation from the average coordinates of approximately 1.1 A for residues 7-27. The structure is consistent with available functional data and shows a spatial separation between known receptor binding determinants and residues found to be outside the hormone-receptor interface.
Solution conformation of an atrial natriuretic peptide variant selective for the type A receptor.,Fairbrother WJ, McDowell RS, Cunningham BC Biochemistry. 1994 Aug 2;33(30):8897-904. PMID:8043577
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.