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Contribution of Cation-\pi Interactions to Protein Stability

Prajapati, Ravindra S and Sirajuddin, Minhajuddin and Durani, Venuka and Sreeramulu, Sridhar and Varadarajan, Raghavan (2006) Contribution of Cation-\pi Interactions to Protein Stability. In: Biochemistry, 45 (50). pp. 15000-15010.

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Abstract

Calculations predict that cation-\pi interactions make an important contribution to protein stability. While there have been some attempts to experimentally measure strengths of cation-\pi interactions using peptide model systems, much less experimental data are available for globular proteins. We have attempted to determine the magnitude of cation-\pi interactions of Lys with aromatic amino acids in four different proteins (LIVBP, MBP, RBP, and Trx). In each case, Lys was replaced with Gln and Met. In a separate series of experiments, the aromatic amino acid in each cation-\pi pair was replaced by Leu.Stabilities of wild-type (WT) and mutant proteins were characterized by both thermal and chemical denaturation. Gln and aromatic \rightarrow Leu mutants were consistently less stable than corresponding Met mutants, reflecting the nonisosteric nature of these substitutions. The strength of the cation-\pi interaction was assessed by the value of the change in the free energy of unfolding [\Delta \Delta G°=\Delta G°(Met)-\Delta G°- (WT)]. This ranged from +1.1 to -1.9 kcal/mol (average value -0.4 kcal/mol) at 298 K and +0.7 to -2.6 kcal/mol (average value -1.1 kcal/mol) at the $T_m$ of each WT. It therefore appears that the strength of cation-\pi interactions increases with temperature. In addition, the experimentally measured values are appreciably smaller in magnitude than calculated values with an average difference $\vert \Delta G^o_{expt}- \Delta G^o_{calc \vert av}$ of 2.9 kcal/mol. At room temperature, the data indicate that cation-\pi interactions are at best weakly stabilizing and in some cases are clearly destabilizing. However, at elevated temperatures, close to typical $T_{m}\hspace{2mm}'s$, cation-\pi interactions are generally stabilizing.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to American Chemical Society.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 30 May 2007
Last Modified: 19 Sep 2010 04:34
URI: http://eprints.iisc.ernet.in/id/eprint/9549

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