Reaction Mechanism of Chorismate Mutase Studied by the Combined Potentials of Quantum Mechanics and Molecular Mechanics

Published

November 21, 2002

Author(s)

Y. S. Lee, S. E. Worthington, Morris Krauss, B R. Brooks

Abstract

The reaction path for the rearrangement of chorismate to prephenate has been determined in a QM/MM study including the entire protein environment while treating the reaction with ab initio quantum chemistry. In addition to the reactant, chorismate, the side-chains of glu78 and arg90 are included in the quantum region to explore whether the strong ionic hydrogen bonding of the side chains to the substrate has a catalytic effect. The hydrogen bond from glu78 induces electronic effects in the cyclohexadienyl ring that activate the substrate. The energetic residue analysis finds that the binding from arg90 is catalytic due to a differential stabilization of the transition state and the local environment along the reaction path. A global QM/MM optimization including the entire protein environment shows only slight changes along the reaction path. This finding offers support for an earlier effective fragment potential study of this reaction, which used a frozen environment. In both studies the rearrangement occurs with almost a complete break in the C-O ether bond in chorismate before the C-C bond in prephenate forms. In this study, the reacting complex forms a hydrogen bond to arg63 and stabilizes the region near the protein surface where the substrate may enter the active site.

Citation

Journal of Physical Chemistry B

Volume

106

Issue

46

Pub Type

Journals

Keywords

ab initio, chorismate mutase, global optimization, QM/MM calculation, reaction path

Citation

Lee, Y. , Worthington, S. , Krauss, M. and Brooks, B. (2002), Reaction Mechanism of Chorismate Mutase Studied by the Combined Potentials of Quantum Mechanics and Molecular Mechanics, Journal of Physical Chemistry B (Accessed December 15, 2024)