EVIDENCE FOR A LOW-TEMPERATURE TRANSITION-STATE BINDING PREFERENCE INBOVINE ADENOSINE-DEAMINASE

Arrhenius plots of the interactions of bovine adenosine deaminase (ADA ) and of coformycin-inhibited ADA with adenosine are non-linear and re veal that coformycin significantly increases the activation energy for reaction only at temperatures well below the normal operating tempera ture of the enzyme (38.3 degrees C). This apparent enhanced affinity o f the enzyme for the transition state analog at low temperature is con firmed from determinations of coformycin binding at 38.3 degrees C (K- I = 5.3 x 10(-11) M) and at 21 degrees C (K-I = 1.1 x 10-(11) M). It i s suggested that these data are inconsistent with a model for general enzyme catalysis that requires an initial transition state complementa ry active site, Instead, it is suggested that an initial active site t ransition 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. (C) 1998 Els evier Science B.V.