How an enzyme surmounts the activation energy barrier
2003
The action of chorismate mutase is a paradigm of enzyme catalysis, because the enzyme is a structurally simple protein that accelerates a straightforward unimolecular reaction: a concerted, intramolecular rearrangement of chorismate to prephenate in which one carbon–carbon bond is formed and one carbon–oxygen bond is broken (Fig. 1). The reaction itself is a vital step in the biosynthesis of aromatic amino acids, lending the enzyme a biological importance equal to its importance in understanding mechanisms of catalysis. In this issue of PNAS, Hur and Bruice (1) have applied the near-attack conformation (NAC) concept, which Bruice and coworkers have been developing for several years (2, 3), to the accelerations produced by several different chorismate mutases, developing thereby what might be called a microhistory of the catalytic process for these enzymes, tracing events between reactant state and transition state. The findings are illuminating and likely to generate considerable surprise.
Fig. 1.
Chorismate rearranges to prephenate: the reaction catalyzed by chorismate mutases. Very roughly and schematically, the structures represent reactive conformers.
Explaining enzyme catalysis has always posed an adequate challenge. Enzymes are powerful catalysts, some accelerating their target reactions by factors that can exceed 1020 (4). Chorismate mutases accelerate their target reaction by ≈106- to 107-fold. The details of how such accelerations are orchestrated in the course of a process in which the enzyme encounters reactant molecules, may, in some cases, shepherd them through various intermediate states to the product molecule(s), and then releases the latter before launching a new catalytic cycle, have been a subject of research, speculation, and debate since the discovery of enzymes.
One of the main conceptual tools for organizing the findings has been Pauling's insight (5) that an enzyme is a biomolecule that specifically binds and thus stabilizes the transition state of the target …
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
15
References
35
Citations
NaN
KQI