The near attack conformation approach to the study of the chorismate to prephenate reaction
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Contributed by Thomas C. Bruice, July 31, 2003
Abstract
Standard free energies (ΔGN°) for formation of near attack conformers, those ground state conformers that can convert directly to the transition state, were calculated for the Claisen rearrangement of chorismate to prephenate in six different environments: water, wild-type enzymes from Bacillus subtilis and Escherichia coli, their Arg90Cit and Glu52Ala mutants, and the 1F7 catalytic antibody. Values of the calculated ΔGN°s and the experimentally determined activation energies (ΔG‡) are linearly related with the slope of ≈1. This demonstrates that the relative rate of the chorismate → prephenate reaction is overwhelmingly dependent on the efficiency of formation of near attack conformers in the ground state.
Footnotes
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↵ † To whom correspondence should be addressed. E-mail: tcbruice{at}chem.ucsb.edu.
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Abbreviations: BsCM, Bacillus subtilis chorismate mutase; EcCM, Escherichia coli chorismate mutase; MD, molecular dynamics; NAC, near attack conformer; TI, thermodynamic integration; TS, transition state; TSA, TS analogue; w-BsCM and w-EcCM, BsCM and EcCM wild-type enzymes.
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See commentary on page 11931.
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↵ § The 20° allowance for Δθ1 matches with the definition (C16 approaching angle <30°) used in refs. 1 and 2. Although θ2 criterion was not explicitly stated in those previous studies, it was taken into account by an inspection of dih1 and dih2.
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↵ ¶ 0.4 kcal/mol (computational) on going from diaxial conformer to IV (2), and 1.4 kcal/mol (experimental) on going from the total ground state to diaxial conformers (13).
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↵ ∥ We use our MD structure of 1F7·TSA instead of the crystal structure, because of the low resolution (3.0 Å) of the crystal structure.
- Copyright © 2003, The National Academy of Sciences
