Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory
Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile...
Gespeichert in:
Veröffentlicht in: | Current Opinion in Chemical Biology 2002-10, Vol.6 (5), p.556-567 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus ‘rebound mechanism’ of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as ‘radicals are both present and absent and the rebound mechanism is both right and wrong’, is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.
The recent controversy surrounding the mechanisms of alkane hydroxylation and alkene epoxidation by cytochrome P-450 is reconciled by use of the two-state reactivity model, which demonstrates that the ultra-short radical lifetimes, deduced from experiment, result from the operation of two states of the enzyme, one of which functions without real radical intermediates. |
---|---|
ISSN: | 1367-5931 1879-0402 |
DOI: | 10.1016/S1367-5931(02)00363-0 |