Binding thermodynamics of the transition state analogue coformycin and of the ground state analogue 1-deazaadenosine to bovine adenosine deaminase

Binding of the transition state analogue coformycin and the ground state an alogue 1-deaazadenosine to bovine adenosine deaminase have been thermodynam ically characterized. The heat capacity changes for coformycin and 1-deazaa denosine binding are -4.7 +/- 0.8 kJ/mole-K and -1.2 +/- 0.1 kJ/mole-K, res pectively. Since the predominant source of heat capacity change in enzyme i nteractions are changes in the extent of exposure of nonpolar amino acid si de chains to the aqueous environment and the hydrophobic effect is the pred ominant factor in native structure stabilization, we propose that the bindi ng of either class of ligand is associated with a stabilizing enzyme confor mational change with coformycin producing the far greater effect. Analysis of the T dependence of the second order rate constant for formation of the enzyme/coformycin complex further reveals that the conformational change is not rate limiting. We propose that the enzyme may facilitate catalysis via the formation of a stabilizing conformation at the reaction transition sta te.