Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry.
The conformation in solution of porcine brain natriuretic peptide was determined by combined use of NMR spectroscopy and distance geometry. A set of 157 inter-proton-distance constraints was derived from the two-dimensional NOE spectra, and further a set of three hydrogen bond constraints was obtained from analysis of the temperature dependence of labile protons. The five structures with minimal violations were selected after performing distance-geometry calculations starting from 40 random initial conformations. The distance-geometry structures were further refined by the use of restrained energy minimization and restrained molecular dynamics. This structure shows a compact conformation with the carboxy-terminal region, Asn21-Tyr26, folded back to the disulfide-linked loop region, Cys4-Cys20. The characteristics of the conformation determined are as follows: conformations of the three segments interposed by glycine residues, which are Arg7-Ile12, Ser14-Leu18 and Cys20-Arg25, were well defined and the segments Arg7-Ile12 and Cys20-Arg25 are rather close to each other and nearly parallel. The biological significance of these local conformations is discussed on the basis of comparisons with those of atrial natriuretic peptide reported by Kobayashi et al.
Inooka
H
H
Tsukuba Research Laboratories, Takeda Chemical Industries Ltd, Ibaraki, Japan.
Kikuchi
T
T
Endo
S
S
Ishibashi
Y
Y
Wakimasu
M
M
Mizuta
E
E
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000648:ultrastructure; D001923:Brain Chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000648:ultrastructure*; D011487:Protein Conformation; D013552:Swine
D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor