Evidence that Water Can Reduce the Kinetic Stability of Protein−Hydrophobic Ligand Interactions

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• 作者：Lan Liu ; Klaus Michelsen ; Elena N. Kitova ; Paul D. Schnier ; John S. Klassen
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：December 22, 2010
• 年：2010
• 卷：132
• 期：50
• 页码：17658-17660
• 全文大小：135K
• 年卷期：v.132,no.50(December 22, 2010)
• ISSN：1520-5126

文摘

The first quantitative comparison of the thermal dissociation rate constants measured for protein−ligand complexes in their hydrated and dehydrated states is described. Rate constants, measured using surface plasmon resonance spectroscopy, are reported for the dissociation of the 1:1 complexes of bovine β-lactoglobulin (Lg) with the fatty acids (FA), palmitic acid (PA), and stearic acid (SA), in aqueous solution at pH 8 and at temperatures ranging from 5 to 45 °C. The rate constants are compared to values determined from time-resolved blackbody infrared radiative dissociation measurements for the gaseous deprotonated (Lg+FA)ⁿ⁻ ions, where n = 6 and 7, at temperatures ranging from 25 to 66 °C. Notably, the hydrated (Lg+PA) complex is kinetically less stable than the corresponding gas phase (Lg+PA)ⁿ⁻ ions at all temperatures investigated; the hydrated (Lg+SA) complex is kinetically less stable than the gaseous (Lg+SA)ⁿ⁻ ions at temperatures <45 °C. The greater kinetic stability of the gaseous (Lg+FA)ⁿ⁻ ions originates from significantly larger, by 11−12 kcal mol⁻¹, E_a values. It is proposed that the differences in the dissociation E_a values measured in solution and the gas phase reflect the differential hydration of the reactant and the dissociative transition state.