Chemistry Reference
In-Depth Information
Figure 13.7
The recognition of
syn
-
conform-
ers of lactose by galectin-1 (Protein Data Bank
fi le 1GZW). The Gal moiety presents both CH-
take place. This is the case for lactose (a) and
the analogous Gal
Φ
β
1,4Xyl
compound
(b).
Galectin-1 also recognizes the Gal
1,3Xyl
isomer in the same conformation (c), but now
the hydrogen bonds involve O4 of the Xyl
residue. The mentioned hydrogen bond interac-
tions are not possible for the other conforma-
tional families.
β
and hydrogen bonding interactions, but the
Glc residue is the key for the exclusive recog-
nition of
syn
-
π
geometries. Indeed, only
for this geometry, hydrogen bonds involving
O3 of the Glc moiety with Glu71 and with Arg48
, syn
-
Φ
Ψ
hydrate-binding proteins may recognize selectively different conformations of the
sugar [10]. In contrast, when protein-sugar contacts are limited to one monosac-
charide residue, the binding site may accommodate different conformations
around the glycosidic bond, providing that there are no steric impediments, and,
consequently, there is no selection of a single conformer of the sugar, as observed
for methyl
β
-allolactoside binding to ricin (see Info Box ) .
13.4
Thermodynamics of Protein- Carbohydrate Interactions
Considering all the preceding information, it becomes clear that, in addition to
the specifi c protein-sugar contacts, other factors govern protein-carbohydrate
interactions. The binding affi nity or, in thermodynamic terms, the Gibbs free
energy of binding (
G °
), is the corollary of the enthalpy/entropy gains and penal-
ties derived from the different events associated with the recognition process. In
detail, the net enthalpy change comprises the favorable contribution of protein-
sugar contacts and all the new water-water hydrogen bonds generated upon
desolvation of protein and sugar, together with the unfavorable contribution of the
breakage of protein-water and sugar-water interactions. Similarly, the net entropy
change includes the entropy gain of water molecules ordered over nonpolar regions
or directly bonded to protein and sugar groups when they return to the bulk, along
with an entropy decrease of the less-ordered perturbed water molecules that
surrounded polar surfaces. In addition, other events imposing entropic penalties
are the restrictions in the translation and overall rotation of the molecules, and
Δ
