Cytochrome P450 reductase Class

The crystal structure of NADPH-cytochrome P450 reductase (CPR), the common electron-transfer protein of Class 11 eukaryotic P450 systems, was reported in 1997. This was followed by the structures of adrenodoxin reductase (AdR) and adrenodoxin (Adx), the two electron-transfer proteins of the Class 1 mitochondrial P450 system. The crystal structure of a cross-linked AdR-Adx complex has also been reported. " Putidaredoxin reductase (PdR) and putidaredoxin (Pd) of the P450cam system have also been structurally characterized. ... 

Figure 13.2. A proposal for a simplified classification of CYPs with reference to either use of a ferredoxin or alternative electron transport mechanism. Class la— typical bacterial system supported by ferredoxin and ferredoxin reductase, for example, CYPlOl Class Ib—Rhodococcus sp. CYP fusion protein containing a ferredoxin domain Class Ic—Methylococcus capsulatus CYPS 1-ferredoxin fusion . Class 11a— typical eukaryotic CYP/NADPH-cytochrome P450 reductase system Class lib—a fusion protein of a CYP and flavoprotein reductase, for example, P450gM 3 Class IIc—P450 j containing separate flavodoxin and flavodoxin reductase partners . Class fll—standalone functional CYPs, for example, P450jj. ...

The cytochrome P450 reductases from class II are thought to be a fusion of a FAD-containing reductase (such as ferredoxin or flavodoxin reductase) and flavodoxin. This family of enzymes includes the flavoprotein subunit of sulfite reductase and the flavoprotein domains of natural fusion proteins such as nitric oxide synthase and P450PM3. The pathway of electron transfer in these enzymes is NADPH -> FAD FMN. The FMN serves as a one-electron donor to cytochrome c. 

The two-domain, structural motif in FNR represents a common structural feature in a large class of enzymes that catalyze electron transfer between a nicotinamide dinucleotide molecule and a one-electron carrier. Beside the photosynthetic electron-transfer enzyme, others non-photosynthetic ones include flavodoxin reductase, sulfite reductase, nitrate reductase, cytochrome reductase, and NADPH-cyto-chrome P450 reductase. FNR belongs to the group of so-called dehydrogenases-electron transferases, i.e., flavoproteins that catalyze electron transfer from two, one-electron donor molecules to a single two-electron acceptor molecule. 

Monooxvgenases. These enzymes are important in the detoxication of pyrethroid, carbamate, organophosphorus and other classes of insecticides (2). They are microsomal, membrane associated enzymes which catalyze reactions in which one atom from molecular oxygen is inserted into the insecticide and the second oxygen atom is reduced to form water. Catalysis depends on the close association of the heme-containing cytochrome P450 terminal oxidase with NADPH cytochrome C reductase for electron transport, and it also depends on availability of NADPH and oxygen. 

Microsomal cytochromes P450 are membrane-bound. They accept electrons from a microsomal NADPH-cytochrome reductase, containing flavin adenine dinucleotide and flavin mononucleotide. All cytochromes P450 metaboUsing drugs and xeno-biotica isolated so far belong to this class. 

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