Energetics of Lipid Binding in a Hydrophobic Protein Cavity

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• 作者：Lan Liu ; Klaus Michelsen ; Elena N. Kitova ; Paul D. Schnier ; John S. Klassen
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：February 15, 2012
• 年：2012
• 卷：134
• 期：6
• 页码：3054-3060
• 全文大小：324K
• 年卷期：v.134,no.6(February 15, 2012)
• ISSN：1520-5126

文摘

Hydrophobic bonding is central to many biochemical processes, such as protein folding and association. However, a complete description of the forces underlying hydrophobic interactions is lacking. The goal of this study was to evaluate the intrinsic energetic contributions of 鈭扖H₃, >CH₂, and 鈭扝C鈺怌H鈥?groups to protein鈥搇ipid binding. To this end, Arrhenius parameters were measured for dissociation of gaseous deprotonated ions (at the 鈭? charge state) of complexes of bovine 尾-lactoglobulin (Lg), a model lipid-binding protein, and a series of saturated, unsaturated, and branched fatty acids (FA). In the gas phase, the (Lg + FA)^{7鈥?/sup> ions adopt one of two noninterconverting structures, which we refer to as the fast and slow dissociating components. The dissociation activation energies measured for the fast components of the (Lg + FA)7鈥?/sup> ions were found to correlate linearly with the association free energies measured in aqueous solution, suggesting that the specific protein鈥搇ipid interactions are preserved in the gas phase. The average contributions that the 鈭扖H₃, >CH₂, and 鈭扝C鈺怌H鈥?groups make to the dissociation activation energies measured for the fast components of the (Lg + FA)7鈥?/sup> ions were compared with enthalpies for the transfer of hydrocarbons from the gas phase to organic solvents. For >CH₂ groups, the interior of the cavity was found to most closely resemble the relatively polar solvents acetone and N,N-dimethylformamide, which have dielectric constants (蔚) of 21 and 39, respectively. For 鈭扖H₃ groups, the solvent environment most closely resembles 1-butanol (蔚 = 17), although the energetic contribution is dependent on the location of the methyl group in the FA. In contrast, the solvation of 鈭扝C鈺怌H鈥?groups is similar to that afforded by the nonpolar solvent cyclohexane (蔚 = 2).}