The mechanism of the catalysis of the Claisen rearrangement of chorismate to prephenate by the chorismate mutase from Bacillus subtilis. A molecular mechanics and hybrid quantum mechanical/molecular mechanical study

Abstract

The role of the active site of the chorismate mutase from Bacillus subtilis in catalysing the Claisen rearrangement of chorismate to prephenate is studied computationally using both molecular mechanics and a hybrid quantum mechanical/molecular mechanical method. Structures along the pathway calculated at the HF/6-31G* level are docked into the active site and reveal that the hydrogen bonding interactions reflect the changing geometry and electronic structure of the substrate. In particular the interactions are maximal close to the transition state and lead to a barrier lowering greater than that needed to produce the observed rate acceleration in line with conclusions that the chemical transformation is not the rate determining process.