Lipopolysaccharide (LPS), the major cell wall constituent of Gram-negative bacteria, evokes a multitude of biological effects in mammals including pyrogenicity and toxic shock syndrome. Polymyxin B (PmB), a polycationic cyclic peptide, is known to neutralize most of its activities. The nature of the interaction of PmB with LPS and lipid A was investigated by isothermal titration calorimetry. PmB binds to LPS as well as lipid A stoichiometrically and non-co-operatively with micromolar affinity. These interactions are driven primarily by a favourable change in entropy (∆S) and are endothermic in nature. These positive changes in enthalpies decrease with increasing temperature, yielding a heat capacity change, ∆Cp, of -2385 J·mol-1·degree-1 for PmB–LPS interactions while the binding of PmB to lipid A displays a ∆Cp of -2259 J·mol-1·degree-1. The negative heat capacity changes provide strong evidence for the role of hydrophobic interactions as the driving force for the association of PmB with LPS and lipid A. A correlation of the energetics of these interactions with analyses of the molecular models of PmB suggests that a cluster of solvent-exposed non-polar amino acid side-chains that line one surface of the molecule, together with a ring of positively charged residues on its other surface, are responsible for its strong and stoichiometric binding to LPS.
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Research Article|
April 15 1996
Titration calorimetric studies to elucidate the specificity of the interactions of polymyxin B with lipopolysaccharides and lipid A
Subita SRIMAL;
Subita SRIMAL
*Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India
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Namita SUROLIA;
Namita SUROLIA
†Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur Post, Bangalore 560 064, India
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S. BALASUBRAMANIAN;
S. BALASUBRAMANIAN
*Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India
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Avadhesha SUROLIA
Avadhesha SUROLIA
‡
*Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India
‡To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 315 (2): 679–686.
Citation
Subita SRIMAL, Namita SUROLIA, S. BALASUBRAMANIAN, Avadhesha SUROLIA; Titration calorimetric studies to elucidate the specificity of the interactions of polymyxin B with lipopolysaccharides and lipid A. Biochem J 15 April 1996; 315 (2): 679–686. doi: https://doi.org/10.1042/bj3150679
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