ISSN:
0006-3525
Keywords:
nuclear Overhauser effect distance constraints
;
torsional angles
;
molecular dynamics calculations
;
conformational model of lipid-bound atrial natriuretic peptide analogue
;
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A conformational study by nmr spectroscopy was performed with the highly active 28-residue hybrid natriuretic peptide analogue pBNP1 [M. Mimeault, A. De Léan, M. Lafleur, D. Bonenfant, and A. Fournier (1995) Biochemistry, Vol. 34, pp. 955-964], which consists of the cyclic peptide core of pBNP32 and the N- and C-terminal exocyclic segments of rANP(99-126). In purely aqueous solution pBNP1 exhibits random coil behavior as evidenced by the almost complete absence of structurally significant nmr observables. By contrast, elements of secondary structure emerged upon the addition of dodecylphosphocholine micelles to the aqueous sample. Nuclear Overhauser effect distance-restrained molecular dynamics simulations in conjunction with torsional angle determinations permitted the generation of a reasonable model of the lipid-bound conformation of pBNP1. According to this model, pBNP1 adopts turn-like features in the cyclic and C-terminal regions of the peptide, but remains quite flexible in the N-terminal segment. Two hydrophobic cores separated by a hydrophilic cleft were also evident in the generated structure. A mechanism is proposed whereby the hydrophobic interactions necessary to stabilize a folded structure of pBNP1 are facilitated by the presence of the membrane-like polar/apolar interface provided by the phospholipid micelles. © 1997 John Wiley & Sons, Biopoly 42: 37-48, 1997
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
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