Intermediates in P450 catalysis

2005 ◽  
Vol 363 (1829) ◽  
pp. 793-806 ◽  
Author(s):  
Thomas L Poulos
Keyword(s):  
Oxygen Atom ◽  
Active Site ◽  
Density Functional Calculations ◽  
Density Functional ◽  
Cytochromes P450 ◽  
Catalytic Cycle ◽  
Nuclear Resonance ◽  
Heme Group ◽  
Electron Paramagnetic

Cytochromes P450 catalyse the insertion of one O 2 -derived oxygen atom in unactivated C–H bonds, and as such, are potent oxidants. A significant amount is known about the P450 catalytic cycle owing partly to the single heme group at the active site that provides spectroscopic handles in tracking various intermediates. A sophisticated array of electron paramagnetic, electron double nuclear resonance, and more traditional absorption spectroscopies have been able to identify key intermediates, while crystallography has defined the structure of the substrate-free, -bound, and oxy-complexes. What has remained elusive is the Fe(IV)=O intermediate, thought to be the active hydroxylating agent. Here, theory and especially density functional calculations have provided valuable insights.

Density Functional Calculations for Modeling the Oxidized States of the Active Site of Nickel−Iron Hydrogenases. 1. Verification of the Method with Paramagnetic Ni and Co Complexes

2002 ◽  
Vol 41 (17) ◽  
pp. 4417-4423 ◽  
Author(s):  
Christian Stadler ◽  
Antonio L. de Lacey ◽  
Belén Hernández ◽  
Víctor M. Fernández ◽  
Jose C. Conesa
Keyword(s):  
Active Site ◽  
Density Functional Calculations ◽  
Density Functional ◽  
Nickel Iron

scholarly journals Hydroxo-Bridged Active Site of Flavodiiron NO Reductase Revealed by Spectroscopy and Computations

2020 ◽  
Author(s):  
Filipe Folgosa ◽  
Vladimir Pelmenschikov ◽  
Matthias Keck ◽  
Christian Lorent ◽  
Yoshitaka Yoda ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Density Functional Theory ◽  
Data Collection ◽  
Active Site ◽  
Density Functional ◽  
Nuclear Resonance ◽  
Structural Studies ◽  
Functional Theory ◽  
Nuclear Resonance Vibrational Spectroscopy ◽  
Ligand Interactions

<p>NO and O<sub>2</sub> are detoxified in many organisms using flavodiiron proteins (FDPs). The exact coordination of the iron centre in the active site of these enzymes remains unclear despite numerous structural studies. Here, we used <sup>57</sup>Fe nuclear resonance vibrational spectroscopy (NRVS) to probe the iron-ligand interactions in <i>Escherichia coli</i> FDP. This data combined with density functional theory (DFT) and <sup>57</sup>Fe Mössbauer spectroscopy indicate that the oxidised form of FDP contains a dihydroxo-diferric Fe(III)–(µOH<sup>–</sup>)<sub>2</sub>–Fe(III) active site, while its reduction gives rise to a monohydroxo-diferrous Fe(II)–(µOH<sup>–</sup>)–Fe(II) site upon elimination of one bridging OH<sup>–</sup> ligand, thereby providing an open coordination site for NO binding. Prolonged NRVS data collection of the oxidised FDP resulted in photoreduction and formation of a partially reduced diiron center with two bridging hydroxyl ligands. These results have crucial implications for studying and understanding the mechanism of FDP as well as other non-haem diiron enzymes.</p>

scholarly journals Density Functional Theory Study into the Reaction Mechanism of Isonitrile Biosynthesis by the Nonheme Iron Enzyme ScoE

2021 ◽  
Author(s):  
Hafiz Saqib Ali ◽  
Sidra Ghafoor ◽  
Sam P. de Visser
Keyword(s):  
Reaction Mechanism ◽  
Hydrogen Atom ◽  
Proton Transfer ◽  
Active Site ◽  
Density Functional ◽  
Active Species ◽  
Nonheme Iron ◽  
Catalytic Cycle ◽  
Hydrogen Atom Abstraction ◽  
Catalytic Cycles

AbstractThe nonheme iron enzyme ScoE catalyzes the biosynthesis of an isonitrile substituent in a peptide chain. To understand details of the reaction mechanism we created a large active site cluster model of 212 atoms that contains substrate, the active oxidant and the first- and second-coordination sphere of the protein and solvent. Several possible reaction mechanisms were tested and it is shown that isonitrile can only be formed through two consecutive catalytic cycles that both use one molecule of dioxygen and α-ketoglutarate. In both cycles the active species is an iron(IV)-oxo species that in the first reaction cycle reacts through two consecutive hydrogen atom abstraction steps: first from the N–H group and thereafter from the C–H group to desaturate the NH-CH2 bond. The alternative ordering of hydrogen atom abstraction steps was also tested but found to be higher in energy. Moreover, the electronic configurations along that pathway implicate an initial hydride transfer followed by proton transfer. We highlight an active site Lys residue that is shown to donate charge in the transition states and influences the relative barrier heights and bifurcation pathways. A second catalytic cycle of the reaction of iron(IV)-oxo with desaturated substrate starts with hydrogen atom abstraction followed by decarboxylation to give isonitrile directly. The catalytic cycle is completed with a proton transfer to iron(II)-hydroxo to generate the iron(II)-water resting state. The work is compared with experimental observation and previous computational studies on this system and put in a larger perspective of nonheme iron chemistry.

Mechanisms for CO oxidation on Fe(iii)–OH–Pt interface: a DFT study

2014 ◽  
Vol 176 ◽  
pp. 381-392 ◽  
Author(s):  
Yun Zhao ◽  
Guangxu Chen ◽  
Nanfeng Zheng ◽  
Gang Fu
Keyword(s):  
Co Oxidation ◽  
Density Functional Calculations ◽  
Density Functional ◽  
Structural Models ◽  
Pt Nanoparticles ◽  
Structure Sensitivity ◽  
Catalytic Cycle ◽  
Dft Study ◽  
Bond Strengths ◽  
Catalytic Cycles

The full catalytic cycle that involves the oxidation of two CO molecules is investigated here by using periodic density functional calculations. To simulate the nature of Fe(OH)x/Pt nanoparticles, three possible structural models, i.e., Fe(OH)x/Pt(111), Fe(OH)x/Pt(332) and Fe(OH)x/Pt(322), are built. We demonstrate that Fe(iii)–OH–Pt stepped sites readily react with CO adsorbed nearby to directly yield CO2 and simultaneously produce coordinatively unsaturated iron sites for O2 activation. By contrast, the created interfacial vacancy on Fe(OH)x/Pt(111) prefers to adsorb CO rather than O2, thus inhabiting the catalytic cycles of CO oxidation. We suggest that such structure sensitivity can be understood in terms of the bond strengths of Fe(iii)–OH.

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