Evidence that water can reduce the kinetic stability of protein-hydrophobic ligand interactions.
J Am Chem Soc
; 132(50): 17658-60, 2010 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-21121620
ABSTRACT
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 11 complexes of bovine ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Água
/
Proteínas
Limite:
Animals
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2010
Tipo de documento:
Article