Strain Effects and Conformational Compression

Strains and conformational compression of the substrate at the enzyme active site were also proposed to explain the rate acceleration by chorismate mutase [66, 70, 

For instance, Jorgensen and his coworkers [78] suggested, based on the results of their calculations and analysis, that the stabilization of the transition state in chorismate mutase plays only a secondary role and that the rate enhancement is primarily due to conformational compress of the substrate. However, the analysis of Jorgensen and coworkers has been called into question [80], and it was shown that the results might be interpreted differently [80]. 

The discussions given in this chapter have shown that although chorismate mutase has been a subject of extensive experimental and theoretical investigations, there are still considerable uncertainties concerning how the Claisen rearrangement from chorismate to prephenate is actually catalyzed by the enzyme. The computational investigations have led different possibilities, but experimental studies with modem techniques are necessary to identify the most likely mechanism of the CM catalysis. 

The work described herein was supported by the Center of Excellence for Structural Biology, University of Tennessee. We thank Prof. Martin Karplus for insightful discussions. 

EcCM Escherichia coli chorismate mutase from P-protein 

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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. 

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