Chorismate electrostatic stabilization

Strajbl M, A Shurki, M Kato, A Warshel (2003) Apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization. J. Am. Chem. Soc. 125 (34) 10228-10237... 

The exact mechanism of the action by chorismate mutase is stUl not clear, in spite of extensive experimental and theoretical investigations. Several suggestions have been proposed concerning the origin of the catalysis. They include (a) the stabilization of transition state by the enzyme, presumably through electrostatic interactions from the active site residues (b) the promotion of substrate conformational transition to generate the reactive CHAIR conformer at the active site (see Scheme 1.2) (c) the increase of populations of near attack conformers (NACs) and (d) strain effects and conformational compression. These proposals will be discussed below. 

This then does a Claisen rearrangement to produce pre-phenate, which is taken on to both Phe and Tyr. The Claisen rearrangement is catalyzed by the enzyme chorismate mutase. The enzyme catalyzes the reaction by as much as a factor of 10 . Extensive mechanistic studies have established that the enzyme-mediated reaction has all the hallmarks of a Claisen rearrangement, including appropriate isotope effects. A major role of the enzyme is to pre-organize chorismate into the proper conformation for rearrangement. However, the enzyme also uses substantial electrostatic interactions to stabilize partial charges in what is a fairly polar pericyclic transition state. 

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