Evidence for a low temperature transition state binding preference in bovine adenosine deaminase

Arrhenius plots of the interactions of bovine adenosine deaminase (ADA) and of coformycin-inhibited ADA with adenosine are non-linear and reveal that coformycin significantly increases the activation energy for reaction only at temperatures well below the normal operating temperature of the enzyme (38.3 degrees C). This apparent enhanced affinity of the enzyme for the transition state analog at low temperature is confirmed from determinations of coformycin binding at 38.3 degrees C (KI = 5.3 x 10(-11) M) and at 21 degrees C (KI = 1.1 x 10(-11) M). It is suggested that these data are inconsistent with a model for general enzyme catalysis that requires an initial transition state complementary active site. Instead, it is suggested that an initial active site transition state complementarity is undesirable and the tendency of the enzyme to exist in this conformer at low temperatures is responsible for its inefficient interaction with adenosine substrate.