Thermodynamics of complex formation between bovine liver glutamate dehydrogenase and analogs of ADP.
A calorimetric study of the thermodynamic parameters for the binding of adenosine, AMP, ADP, and ATP to L-glutamate dehydrogenase shows that the variation of deltaG0 of binding is quite small and is correlated qualitatively both with the effectiveness of these ribonucleotides as activators of the L-glutamate dehydrogenase reaction and with size (for the first three). Much larger variations are observed for the deltaH0 of binding largely compensated by changes in deltaS0, with a zig-zag dependence on the number of phosphate groups. For comparison, the binding parameters are also obtained for the deoxyribose analogs of these compounds as well as cyclic adenosine 3':5'-monophosphate and purine riboside. Salt concentration and buffer composition were shown to affect mainly the entropy changes for ADP binding; and the deltaCp values for binding of AMP and ADP to the enzyme are quite small. It is suggested that the general area of the enzyme surface which includes the binding sites for ADP and its analogs contains a number of functional groups, each capable of an energetically small interaction with some group on one or more of the ligands, but so located that even the largest ligand cannot interact with all of them simultaneously. Each ligand minimizes the free energy of the system by selecting the best pattern of such individual interactions permitted by its geometry. Such a pattern of microheterogeneity of ligand-protein interactions may be a major source of the known specificity of binding in biological systems.
D000241:Adenosine; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives*; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000818:Animals; D001665:Binding Sites; D002151:Calorimetry; D002417:Cattle; D003854:Deoxyribonucleotides; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000201:enzymology*; D008433:Mathematics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D003854:Deoxyribonucleotides; D008024:Ligands; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005969:Glutamate Dehydrogenase; D000241:Adenosine