title: The differences in conformation between alpha-human atrial natriuretic polypeptide, alpha-hANP, and its derivative, Met(O)-alpha-hANP, in solution.
abstract: The differences in conformation between alpha-human atrial natriuretic polypeptide (alpha-hANP) and its inactive analog, Met(O)-alpha-hANP, have been analyzed by nuclear magnetic resonance spectroscopy. All proton resonances for both peptides were assigned by means of the sequential assignment procedure. The three-dimensional structure of alpha-hANP in solution had previously been determined by distance geometry calculation using distance constraints derived from nuclear Overhauser effects (NOEs). Here, the three-dimensional structure of Met(O)-alpha-hANP was determined. The conformational differences between these two molecules were as follows: three segments of alpha-hANP, Ser1-Cys7, Arg11-Ala17 and Gln18-Tyr28, have some ordered structures. In Met(O)-alpha-hANP the Gln18-Tyr28 region has a similar conformation, while the remaining two regions do not have the ordered structure found in alpha-hANP. It is suggested that the conserved conformation of the Gln18-Tyr28 region is required for binding to the ANP receptor and that the slight biological activity of Met(O)-alpha-hANP is due to loss of the ordered structures evoked in the Ser1-Cys7 and Arg11-Ala17 regions of alpha-hANP.
authors: Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors: S
authors: S
authors: Koyama
authors: Y
authors: Y
authors: Kobayashi
authors: T
authors: T
authors: Ohkubo
authors: Y
authors: Y
authors: Kyogoku
authors: A
authors: A
authors: Sato
authors: M
authors: M
authors: Kobayashi
authors: N
authors: N
authors: Go
mesh_terms: D000595:Amino Acid Sequence; D009320:Atrial Natriuretic Factor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D011487:Protein Conformation
chemical_list: D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor