Contribution of cation-π interactions to protein stability

Prajapati, Ravindra S. ; Sirajuddin, Minhajuddin ; Durani, Venuka ; Sreeramulu, Sridhar ; Varadarajan, Raghavan (2006) Contribution of cation-π interactions to protein stability Biochemistry, 45 (50). pp. 15000-15010. ISSN 0006-2960

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Official URL: http://pubs.acs.org/doi/abs/10.1021/bi061275f

Related URL: http://dx.doi.org/10.1021/bi061275f

Abstract

Calculations predict that cation-π interactions make an important contribution to protein stability. While there have been some attempts to experimentally measure strengths of cation-p interactions using peptide model systems, much less experimental data are available for globular proteins. We have attempted to determine the magnitude of cation-π 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-p pair was replaced by Leu. Stabilities of wild-type (WT) and mutant proteins were characterized by both thermal and chemical denaturation. Gln and aromatic → Leu mutants were consistently less stable than corresponding Met mutants, reflecting the nonisosteric nature of these substitutions. The strength of the cation-π interaction was assessed by the value of the change in the free energy of unfolding [ΔΔ G° = Δ G°(Met) - Δ 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 Tm of each WT. It therefore appears that the strength of cation-π interactions increases with temperature. In addition, the experimentally measured values are appreciably smaller in magnitude than calculated values with an average difference |Δ G°expt - Δ G°calc|av of 2.9 kcal/mol. At room temperature, the data indicate that cation-π interactions are at best weakly stabilizing and in some cases are clearly destabilizing. However, at elevated temperatures, close to typical Tm's, cation-π interactions are generally stabilizing.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society.
ID Code:57278
Deposited On:26 Aug 2011 04:20
Last Modified:26 Aug 2011 04:20

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