Bhattacharjya, Surajit and David, Sunil A and Mathan, VI and Balaram, P (1997) Polymyxin B Nonapeptide: Conformations in Water and in the Lipopolysaccharide-Bound State Determined by Two-Dimensional NMR and Molecular Dynamics. In: Biopolymers, 41 (3). pp. 251-265.
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Polymyxin B nonapeptide (PMN) is a derivative of polymyxin B, an alpha, gamma-diaminobutyric acid-rich decapeptide from Bacillus polymyxa that displays antimicrobial and lipopolysaccharide (LPS)-antagonistic activities. The conformations of PMN in aqueous solution as well as in the LPS-bound state have been studied by 1H two-dimensional nmr methods in conjunction with molecular dynamics techniques. The aqueous structure of the free peptide is characterized by a type II beta-turn centered around D-Phe5 and Leu6, and an inverse -turn at Thr9. The LPS-bound conformation of PMN was studied by transferred nuclear Overhauser effect experiments. The essential features of the cyclic portion of free aqueous PMN are mostly preserved when the peptide is bound to LPS; however, the linear dipeptide fragment as well as the side chains of the heptatpeptide ring show a conformational change and a reduction in mobility. The LPS-bound PMN structure was used to construct a model of the lipid A-polymyxin B (decapeptide) complex, which allows the rationalization of several experimental observations concerning the binding of polymyxin to, and consequent neutralization of, the toxicity of LPS, and may be of value in the rational therapeutic targeting of endotoxin.
|Item Type:||Journal Article|
|Additional Information:||Copyright for this article belongs to John Wiley & Sons, Inc.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||28 Oct 2004|
|Last Modified:||19 Sep 2010 04:17|
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