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Fluoroalcohols as structure modifiers in peptides and proteins: hexafluoroacetone hydrate stabilizes a helical conformation of melittin at low pH

Bhattacharjya, S and Venkatraman, J and Balaram, P and Kumar, A (1999) Fluoroalcohols as structure modifiers in peptides and proteins: hexafluoroacetone hydrate stabilizes a helical conformation of melittin at low pH. In: Journal of Peptide Research, 54 (2). pp. 100-111.

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Official URL: http://onlinelibrary.wiley.com/doi/10.1034/j.1399-...

Abstract

The effect of hexafluoroacetone hydrate (HFA) on the structure of the honey bee venom peptide melittin has been investigated. In aqueous solution at low pH melittin is predominantly unstructured. Addition of HFA at pH = 2.0 induces a structural transition from the unstructured state to a predominantly helical conformation as suggested by intense diagnostic far UV CD bands. The structural transition is highly cooperative and complete at 3.6 M (50% v/v) HFA. A similar structural transition is also observed in 2,2,2 trifluoroethanol which is complete only at a cosolvent concentration of 8 M. Temperature dependent CD experiments support a 'cold denaturation' of melittin at low concentrations of HFA, suggesting that selective solvation of peptide by HFA is mediated by hydrophobic interactions. NMR studies in 3.6 M HFA establish a well defined helical structure of melittin at low pH, as suggested by the presence of strong NHi/NHi+1 NOEs throughout the sequence, along with many medium range helical NOEs. Structure calculations using NOE driven distance constraints reveal a well ordered helical fold with a relatively flexible segment around residues T10-G11-T12. The helical structure of melittin obtained at 3.6 M HFA at low pH is similar to those determined in methanolic solution and perdeuterated dodecylphosphocholine micelles. HFA as a cosolvent facilitates helix formation even in the highly charged C terminal segment.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to Blackwell Publishing.
Keywords: Fluoroalcohols;Helix stabilization;Hexafluoroacetone;Melittin;Specific solvation
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 28 Sep 2004
Last Modified: 13 Jan 2012 07:52
URI: http://eprints.iisc.ernet.in/id/eprint/2069

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