Apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization

Marek Štrajbl, Avital Shurki, Mitsunori Kato, Arieh Warshel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

The catalytic reaction of chorismate mutase (CM) has been the subject of major current attention. Nevertheless, the origin of the catalytic power of CM remains an open question. In particular, it has not been clear whether the enzyme works by providing electrostatic transition state stabilization (TSS), by applying steric strain, or by populating near attack conformation (NAC). The present work explores this issue by a systematic quantitative analysis. The overall catalytic effect is reproduced by the empirical valence bond (EVB) method. In addition, the binding free energy of the ground state and the transition state is evaluated, demonstrating that the enzyme works by TSS. Furthermore, the evaluation of the electrostatic contribution to the reduction of the activation energy establishes that the TSS results from electrostatic effects. It is also found that the apparent NAC effect is not the reason for the catalytic effect but the result of the TSS. It is concluded that in CM as in other enzymes the key catalytic effect is electrostatic TSS. However, since the charge distribution of the transition state and the reactant state is similar, the stabilization of the transition state leads to reduction in the distance between the reacting atoms in the reactant state.

Original languageAmerican English
Pages (from-to)10228-10237
Number of pages10
JournalJournal of the American Chemical Society
Volume125
Issue number34
DOIs
StatePublished - 27 Aug 2003
Externally publishedYes

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