Psychrophilic enzymes: revisiting the thermodynamic parameters of activation may explain local flexibility

Abstract

Basic theoretical and practical aspects of activation parameters are briefly reviewed in the context of cold-adaptation. In order to reduce the error impact inherent to the transition state theory on the absolute values of the free energy (Δ G #), enthalpy (Δ H #) and entropy (Δ S #) of activation, it is proposed to compare the variation of these parameters between psychrophilic and mesophilic enzymes, namely Δ(Δ G #) p–m, Δ(Δ H #) p–m and Δ(Δ S #) p–m. Calculation of these parameters from the available literature shows that the main adaptation of psychrophilic enzymes lies in a significant decrease of Δ H #, therefore leading to a higher k cat, especially at low temperatures. Moreover, in all cases including cold-blooded animals, Δ S # exerts an opposite and negative effect on the gain in k cat. It is argued that the magnitude of this counter-effect of Δ S # can be reduced by keeping some stable domains, while increasing the flexibility of the structures required to improve catalysis at low temperature, as demonstrated in several cold-active enzymes. This enthalpic-entropic balance provides a new approach explaining the two types of conformational stability detected by recent microcalorimetric experiments on psychrophilic enzymes.