The interpretation of site-directed mutagenesis experiments by linear free energy relations

Fersht and co-workers have applied a linear free energy relation(Brønsted equation) to analyze site-directed mutagenesisexperiments involving the enzyme tyrosyl-tRNA synthetase andhave suggested that the Brønsted exponent is linearlycorrelated with the value of the reaction coordinate at thetransition state. We point out that when the mutants differsolely through the formation or deletion of a hydrogen bondaway from the reaction center, a linear free energy relationis expected only in limiting cases for which the Brønstedrelation exponent is 0, 1 or . The results may be correlatedwith a conformational coordinate but not with the developmentof the reaction coordinate per se.