The High-Valent Compound of Cytochrome P450: The Nature of the Fe−S Bond and the Role of the Thiolate Ligand as an Internal Electron Donor

The intermediates operating in the cytochrome P450 catalytic cycle have been investigated for more than half a century, fascinating many enzymologists. Each intermediate has its unique role to carry out diverse oxidations. Natural time course of the catalytic cycle is quite fast, hence, not all of the reactive intermediates could be isolated during physiological catalysis. Different high-valent iron intermediates have been proposed as primary oxidants: the candidates are compound 0 (Cpd 0, [FeOOH][Formula: see text]P450) and compound I (Cpd I, Fe(IV)[Formula: see text]O por[Formula: see text]P450). Among them, the role of Cpd I in hydroxylation is fairly well understood due the discovery of the peroxide shunt. This review endeavors to put the outstanding research efforts conducted to isolate and characterize the intermediates together. In addition to spectral features of each intermediate in the catalytic cycle, the oxidizing powers of Cpd 0 and Cpd I will be discussed along with most recent scientific findings.

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Experimental and Computational Approaches on the Isospecific Role of Monoester-Type Internal Electron Donor for TiCl4/MgCl2 Ziegler-Natta Catalysts

Macromolecular Symposia ◽

10.1002/masy.200751407 ◽

2007 ◽

Vol 260 (1) ◽

pp. 42-48 ◽

Cited By ~ 12

Author(s):

Boping Liu ◽

Ruihua Cheng ◽

Zhen Liu ◽

Pengyuan Qiu ◽

Shiliang Zhang ◽

...

Keyword(s):

Electron Donor ◽

Computational Approaches ◽

Internal Electron ◽

Ziegler Natta Catalysts

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Role of the interface between the FMN and FAD domains in the control of redox potential and electronic transfer of NADPH–cytochrome P450 reductase

Biochemical Journal ◽

10.1042/bj20101984 ◽

2011 ◽

Vol 435 (1) ◽

pp. 197-206 ◽

Cited By ~ 24

Author(s):

Louise Aigrain ◽

Denis Pompon ◽

Gilles Truan

Keyword(s):

Electron Transfer ◽

Cytochrome P450 ◽

Cytochrome P450 Reductase ◽

Nadph Cytochrome ◽

Catalytic Domains ◽

P450 Reductase ◽

Internal Electron ◽

Nadph Cytochrome P450 Reductase ◽

The Impact

CPR (NADPH–cytochrome P450 reductase) is a multidomain protein containing two flavin-containing domains joined by a connecting domain thought to control the necessary movements of the catalytic domains during electronic cycles. We present a detailed biochemical analysis of two chimaeric CPRs composed of the association of human or yeast FMN with the alternative connecting/FAD domains. Despite the assembly of domains having a relatively large evolutionary distance between them, our data support the idea that the integrity of the catalytic cycle is conserved in our chimaeric enzymes, whereas the recognition, interactions and positioning of both catalytic domains are probably modified. The main consequences of the chimaerogenesis are a decrease in the internal electron-transfer rate between both flavins correlated with changes in the geometry of chimaeric CPRs in solution. Results of the present study highlight the role of the linker and connecting domain in the recognition at the interfaces between the catalytic domains and the impact of interdomain interactions on the redox potentials of the flavins, the internal electron-transfer efficiency and the global conformation and dynamic equilibrium of the CPRs.

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Pharmacogenetics of Clozapine: In Vivo Role of Cytochrome P450 Isoforms and P-Glycoprotein

Pharmacopsychiatry ◽

10.1055/s-0028-1088256 ◽

2008 ◽

Vol 41 (05) ◽

Author(s):

E Jaquenoud-Sirot ◽

B Knezevic ◽

G Perla Morena ◽

P Baumann ◽

CB Eap

Keyword(s):

Cytochrome P450 ◽

P Glycoprotein ◽

Cytochrome P450 Isoforms

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