Enzyme catalysis quantitative aspects

The importance of protein electrostatics was pointed out and demonstrated by others quite early (e.g. Perutz, 1978 Hoi et al., 1978 Naray-Szaob, 1979) using more qualitative considerations, and it starts to be widely accepted (cf. e.g. Sharp and Honig, 1990). Here we will try to provide several examples for the importance of such effects in enzyme catalysis and in other aspects of protein action. We will try to distinguish between very qualitative treatments that do not consider the complete environment and quantitative ones treating it correctly. This is quite crucial, since the basic issue in enzyme catalysis is the actual magnitude of the given effect and not the assumption that it can be operative in some cases. 

The two quantities, catalytic proficiency (which has the dimensions in the example above) and rate enhancement (which is dimensionless in the example above), give a valid account of two aspects of enzyme catalysis. The catalytic proficiency, as the equilibrium constant for transition-state binding to the free enzyme, measures quantitatively the affinity of the free enzyme for the transition state. The free-energy equivalent of the catalytic proficiency gives the total transition-state stabilization by the enzyme. The rate enhancement, as the equilibrium constant for the expulsion of a substrate molecule from the active site of the enzyme and its replacement by a transition-state molecule, quantitatively describes the relative affinity of the enzyme for the transition state compared to the reactant-state substrate. 

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