Question

Identify enzyme structural features that will increase the rate of an enzymatic reaction based on transition state theory.

Answer 1

We have introduced the “enzymatic shielding” concept that summarizes this and other differences between enzymatic reaction and reaction in solution, resulting in an increased reaction rate: less reorganization of the environment, smaller participation of environmental degrees of freedom during the barrier crossing, and finally reduced nonequilibrium effects. Although further research may be required to generalize these conclusions, some of the results presented here have been already observed in systems involving larger charge redistributions. In particular, the methyl transfer reaction catalyzed by catechol O-methyl transferase (COMT) proceeds from charged reactants (catecholate and S-adenosyl methionine) to neutral products. In that case it was found that the transmission coefficient for the enzymatic TS defined using a simple antisymmetric transfer coordinate was quite high (52). In addition, the quality of the RC, determined from the committor histogram, was not noticeably improved when optimized, including also a collective environmental coordinate. Instead, the quality of the RC was noticeably improved when the same procedure was followed for the counterpart process in solution.