The catalytic pathway of cytochrome p450cam at atomic resolution.

@article{Schlichting2000TheCP,
  title={The catalytic pathway of cytochrome p450cam at atomic resolution.},
  author={I. Schlichting and J. Berendzen and K. Chu and Ann M Stock and S. Maves and D. E. Benson and R. Sweet and D. Ringe and G. Petsko and S. Sligar},
  journal={Science},
  year={2000},
  volume={287 5458},
  pages={
          1615-22
        }
}
Members of the cytochrome P450 superfamily catalyze the addition of molecular oxygen to nonactivated hydrocarbons at physiological temperature-a reaction that requires high temperature to proceed in the absence of a catalyst. Structures were obtained for three intermediates in the hydroxylation reaction of camphor by P450cam with trapping techniques and cryocrystallography. The structure of the ferrous dioxygen adduct of P450cam was determined with 0.91 angstrom wavelength x-rays; irradiation… Expand
MECHANISTIC ENZYMOLOGY OF OXYGEN ACTIVATION BY THE CYTOCHROMES P450
TLDR
The detailed mechanism of P450 dioxygen scission is discussed utilizing the CYP101 hydroxylation of camphor as a model system and a structural and spectroscopic analysis of the nature of critical intermediate states in the reaction is discussed. Expand
Intermediates in P450 catalysis
  • T. Poulos
  • Chemistry, Medicine
  • Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
  • 2005
Cytochromes P450 catalyse the insertion of one O2-derived oxygen atom in unactivated C–H bonds, and as such, are potent oxidants. A significant amount is known about the P450 catalytic cycle owingExpand
Activation of Molecular Oxygen in Cytochromes P450
The complex multistep mechanism of oxygen activation in P450 is reviewed as a sequence of the following reactions: Substrate binding, reduction of the heme iron from ferric to the ferrous state,Expand
Heme and oxygen: intermediates on the pathway to substrate oxygenation
Abstract In this tribute to the contributions of Professor Osamu Hayaishi, recent advances in structural biology, radiation chemistry and cryobiochemistry have been used to observe, characterize andExpand
Quantum chemical studies of methane monooxygenase: comparision with P450.
TLDR
The catalytic pathways of soluble methane monooxygenase (sMMO) and cytochrome P450CAM, iron-containing enzymes, are described and compared and the role played by the protein in each system is compared. Expand
Mechanisms of reaction in cytochrome P450: Hydroxylation of camphor in P450cam.
The fundamental nature of reactivity in cytochrome P450 enzymes is currently controversial. Modelling of bacterial P450cam has suggested an important role for the haem propionates in the catalysis,Expand
The Proton Relay Network in the Bacterial P450s: CYP101A1 and CYP101D1.
TLDR
A series of mutagenic, crystallographic, kinetic and molecular dynamics studies indicate that this mutation locks P450cam into a closed inactive conformation, opening a window into the critical proton coupled electron step in P450 catalysis. Expand
Oxygen activation by cytochrome P450 monooxygenase
TLDR
Recent advances in understanding the molecular mechanisms by which P450 activates dioxygen are reviewed, finding similarities to PSII in proton delivery networks, oxygen and water access channels, and consecutive electron transfer processes. Expand
Delicate conformational balance of the redox enzyme cytochrome P450cam
TLDR
Using paramagnetic NMR spectroscopy with a lanthanoid tag, it is shown that the enzyme bound to its redox partner, putidaredoxin, is in a closed state at ambient temperature in solution, which supports a model of catalysis in which the substrate is locked in the active site pocket and the enzyme acts as an insulator for the reactive intermediates of the reaction. Expand
Peripheral heme substituents control the hydrogen-atom abstraction chemistry in cytochromes P450
TLDR
The results reveal that the enzyme catalyzes the hydrogen-atom abstraction step with a remarkably low free-energy barrier, providing a satisfactory explanation for the experimental failure to trap the proposed catalytically competent high-valent heme Fe(IV) oxo (oxyferryl) species responsible for this hydroxylation chemistry. Expand
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