The Thermodynamics of Protein-Carbohydrate Interaction

Having considered those intermolecular interactions that contribute to overall net measured thermodynamic parameters, we turn now to a review of thermodynamic measurements of protein-carbohydrate binding reported during the last five years. Values reported prior to this time can be found in earlier reviews. Calorimetrically derived changes in enthalpies, entropies, free energies and molar heat capacity that occur during protein-carbohydrate binding are shown in Table 8. 

Andthrombin III Antithrombin III K AA Andthrombin III K AA Andthrombin III R AQ Andthrombin III K AA CBDNl 

FGF-1 cyclic mimic FGF-1 Native Binding Site FGF-1 D-Prol36 Gal-1 (Bovine Spleen) 

1 -Deoxynojirimycin Clorobiocin Novobiocin PGlcNAc(l-PGlcNAc(l-aGluOPh IdGlu aGluF 

Previously, we and others have commented on the similarities and differences between patterns of saccharide association for lectins and antibodies [3]. Unfortunately, the database of thermodynamic parameters for antibody-carbohydrate complexation remains small. While important structural and energetic differences may exist that provide clues to the origin of both affinity and association in aqueous solution, it is impossible to reach any conclusions at this time. 

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The small size of hevein (43 residues), and the ease of its availability by biochemical purification or methods of peptide synthesis make this domain an excellent model system for the study of carbohydrate recognition by proteins. Herein, and taking the hevein domain as a model, we focus on the study of those molecular-recognition features relevant for the interactions between carbohydrates and proteins. We detail all of the techniques that are instrumental for tackling this problem, and how these can strategically be combined in an efficient manner. Particular emphasis is placed on the acquisition and analysis of data at atomic resolution (by NMR and/or X-ray ), and how these structural data relate with thermodynamic and kinetic information in reaching an understanding of the forces and interactions that play decisive roles in the interactions between carbohydrates and proteins. 

The decrease in entropy that is usually observed in carbohydrate-protein interactions could partly be due to the restriction of conformational mobility of the substrate on complex formation. Also, effects of complex formation on the conformational changes in the protein should affect the overall thermodynamics of binding. Reinforcement of interactions that stabilize the overall protein conformation during substrate binding can contribute to the exothermicity of the reaction, for example, while rigidification of the peptide chain or reduction of the mobility of the functional groups inside the active center should have an adverse effect on entropy. 

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