Substrate conformational transitions in the active site of chorismate mutase: their role in the catalytic mechanism.

Abstract:

:Chorismate mutase acts at the first branch-point of aromatic amino acid biosynthesis and catalyzes the conversion of chorismate to prephenate. The results of molecular dynamics simulations of the substrate in solution and in the active site of chorismate mutase are reported. Two nonreactive conformers of chorismate are found to be more stable than the reactive pseudodiaxial chair conformer in solution. It is shown by QM/MM molecular dynamics simulations, which take into account the motions of the enzyme, that when these inactive conformers are bound to the active site, they are rapidly converted to the reactive chair conformer. This result suggests that one contribution of the enzyme is to bind the more prevalent nonreactive conformers and transform them into the active form in a step before the chemical reaction. The motion of the reactive chair conformer in the active site calculated by using the QM/MM potential generates transient structures that are closer to the transition state than is the stable CHAIR conformer.

authors

Guo H,Cui Q,Lipscomb WN,Karplus M

doi

10.1073/pnas.141230998

keywords:

subject

Has Abstract

pub_date

2001-07-31 00:00:00

pages

9032-7

issue

16

eissn

0027-8424

issn

1091-6490

pii

98/16/9032

journal_volume

98

pub_type

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