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

被引:27
作者
Liu, Lan [1 ]
Michelsen, Klaus [2 ]
Kitova, Elena N. [1 ]
Schnier, Paul D. [2 ]
Klassen, John S. [1 ]
机构
[1] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada
[2] Amgen Inc, Mol Struct, Thousand Oaks, CA 91320 USA
基金
加拿大自然科学与工程研究理事会;
关键词
BETA-LACTOGLOBULIN; INTERMOLECULAR INTERACTIONS; MASS-SPECTROMETRY; GAS-PHASE; BINDING; COMPLEXES; CAVITY;
D O I
10.1021/ja106731e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 beta-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 degrees 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 degrees 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 degrees 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.
引用
收藏
页码:17658 / 17660
页数:3
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