Principles of Protein Carbohydrate Recognition

Basically, typical contributions to the Gibbs' free energy of ligand binding originate from hydrogen bonding, van der Waals forces and the consequences of the hydrophobic effect. Factors to be reckoned with to predict the affinity of a ligand further include any alterations of the geometry and motional dynamics of the receptor and/or the ligand and/or the solvent molecules. As experimentally readily accessible parameters by calorimetric techniques, the determination of the reaction enthalpy and entropy delineates the global driving force towards complex formation. These parameters have, for example, been measured for an array of mono- and disaccharides in the cases of a plant and an animal lectin sharing specificity to D-galactose (Bharadwaj et al., 1999), and the plot of the data (Fig. 5) according to the equation:

Fig. 5 Enthalpy-entropy compensation plot for the binding of a panel of mono- and disaccharides to the galactoside-specific mistletoe lectin (•) and the galectin from adult chicken liver (o)

Fig. 5 Enthalpy-entropy compensation plot for the binding of a panel of mono- and disaccharides to the galactoside-specific mistletoe lectin (•) and the galectin from adult chicken liver (o)

reveals a slope near unity and intercepts of -16.45 kJ/mol (plant lectin) and -23.12 kJ/mol (animal lectin).

This figure conveys a fundamental message on the relation between enthalpic and entropic factors attributed to the participation of weak intermolecular forces. An increase in enthalpy for ligand binding is inherently balanced by an entropic penalty (or vice versa), an obvious example of common enthalpy-entropy compensation (Dunitz, 1995; Gilli et al., 1994; Lumry and Rajender, 1970). Its illustration automatically poses an ambitious question. The major challenge is to assign events on the level of the molecules in the course of association to the global enthalpic and entropic factors to bridge the gap between the demand for rules to optimize shape recognition and the thermodynamics. With this knowledge in hand, it might be feasible to intentionally shift the specificity and selectivity of derivatives. As the controversial discussion on the positive or negative role of water molecules for the enthalpy of complexation illuminates (Gabius, 1998; García-Hernández and Hernández-Arana, 1999; Lemieux, 1996; Toone, 1994), it will be essential to scrutinize the behavior of each participant of the molecular rendezvous in detail. Consequently, quick complete answers should not be expected but stepwise advances by the combination of computer-assisted calculations, spectroscopic techniques in solution, chemical tinkering with the ligand structure towards potent mimetics, and x-ray crystallography. An impression into the practical implementation of this interdisciplinary approach is given in the next paragraph.

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Getting Started With Solar

Getting Started With Solar

Do we really want the one thing that gives us its resources unconditionally to suffer even more than it is suffering now? Nature, is a part of our being from the earliest human days. We respect Nature and it gives us its bounty, but in the recent past greedy money hungry corporations have made us all so destructive, so wasteful.

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