T. Lundback et T. Hard, SEQUENCE-SPECIFIC DNA-BINDING DOMINATED BY DEHYDRATION, Proceedings of the National Academy of Sciences of the United Statesof America, 93(10), 1996, pp. 4754-4759
qFluorescence spectroscopy and isothermal titration calorimetry were u
sed to study the thermodynamics of binding of the glucocorticoid recep
tor DNA-binding domain to four different, but similar, DNA-binding sit
es. The binding sites are two naturally occurring sites that differ in
the composition of one base pair, i.e., A . T to G . C mutation, and
two sites containing chemical intermediates of these base pairs. The c
alorimetrically determined heat capacity change (Delta C-p degrees(obs
)) for glucocorticoid receptor DNA-binding domain binding agrees with
that calculated for dehydration or solvent-accessible surface areas. A
dominating effect of dehydration or solvent reorganization on the the
rmodynamics is also consistent with an observed linear relationship be
tween observed enthalpy change (Delta H degrees(obs)) and observed ent
ropy change (Delta S degrees(obs)) with a slope close to the experimen
tal temperature. Comparisons with structural data allow us to rational
ize individual differences between Delta H degrees(obs) (and Delta S d
egrees(obs)) for the four complexes. For instance, we find that the re
moval of a methyl group at the DNA-protein interface is enthalpically
favorable but entropically unfavorable, which is consistent with a rep
lacement by an ordered water molecule.