P450-containing Systems

Any enzyme system that includes cytochrome P450 protein or domain can be called a P450-containing system.

P450 enzymes usually function as a terminal oxidase in multicomponent electron-transfer chains, called P450-containing monooxygenase systems, although self-sufficient, non-monooxygenase P450s have been also described. All known P450-containing monooxygenase systems share common structural and functional domain architecture. Apart from the cytochrome itself, these systems contain one or more fundamental redox domains: FAD-containing flavoprotein or domain, FMN domain, ferredoxin and cytochrome ''b''₅. These ubiquitous redox domains, in various combinations, are widely distributed in biological systems. FMN domain, ferredoxin or cytochrome ''b''₅ transfer electrons between the flavin reductase (protein or domain) and P450. While P450-containing systems are found throughout all kingdoms of life, some organisms lack one or more of these redox domains.

FR/Fd/P450 systems

Mitochondrial and some bacterial P450 systems employ soluble Fe₂S₂ ferredoxins (Fd) that act as single electron carriers between FAD-containing ferredoxin reductase (FR) and P450. In mitochondrial monooxygenase systems, adrenodoxin functions as a soluble electron carrier between NADPH: adrenodoxin reductase and several membrane-bound P450s (CYP11A, CYP11B, CYP27). In bacteria, putidaredoxin, terpredoxin, and rhodocoxin serve as electron carriers between corresponding NADH-dependent ferredoxin reductases and soluble P450s ( CYP101, CYP108, CYP116).

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The general scheme of electron flow in the P450 systems containing adrenodoxin-type ferredoxins is:

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CPR/P450 systems

Eukaryotic microsomal P450 enzymes and some bacterial P450s receive electrons from a FAD- and FMN-containing enzyme known as cytochrome P450 reductase (CPR; ). Microsomal CPR is membrane-bound protein that interacts with different P450s. In ''Bacillus megaterium'' and ''Bacillus subtilis'', CPR is a C-terminal domain of CYP102, a single polypeptide self-sufficient soluble P450 system (P450 is an N-terminal domain). The general scheme of electron flow in the CPR/P450 system is:

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CBR/b5/P450 systems

The ubiquitous electron-transport protein cytochrome ''b''₅ can serve as an effector (activator or inhibitor) of P450s. It was hypothesized that cytochrome ''b''₅ is involved in the transfer of the ''second'' electron to P450, either from CPR or from NADH:cytochrome ''b''₅ reductase (CBR; ):

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The ability of the CBR/cytochrome ''b''₅ system to support P450 catalysis has been demonstrated ''in vitro'' using purified CBR and cytochrome ''b''₅ from ''Saccharomyces cerevisiae'' and CYP51 enzyme from ''Candida albicans''. In this system, ''both'' the first and second electrons are donated by CBR.

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FMN/Fd/P450 systems

An unusual one-component P450 system was originally found in ''Rhodococcus'' sp. NCIMB 9784
CYP116B2
. In this system, the N-terminal P450 domain is fused to the reductase domain that shows sequence similarity to phthalate dioxygenase reductase and consists, in its turn, of FMN-binding domain and C-terminal plant-type ferredoxin domain. Similar systems have been identified in the heavy-metal-tolerant bacterium ''Ralstonia metallidurans''
CYP116A1
and in several species of ''Burkolderia''.
The general scheme of electron flow in this system appears to be:

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P450-only systems

Nitric oxide reductase (P450nor) is a P450 enzyme involved in denitrification in several fungal species. The best-characterized P450nor i
CYP55A1
from '' Fusarium oxysporum''. This enzyme does not have monooxygenase activity but is able to reduce nitric oxide (NO^·) to form nitrous oxide (N₂O) directly using NAD(P)H as electron donor:

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Fatty acid β-hydroxylase P450_BSβ from ''Bacillus subtilis''
CYP152A1
and fatty acid α-hydroxylase P450_SPα from '' Pseudomonas paucimobilis''
CYP152B1
catalyse the hydroxylation reaction of long-chain fatty acids using hydrogen peroxide (H₂O₂) as an oxidant. These enzymes do not require any reduction system for catalysis.

Allene oxide synthase (CYP74A; ), fatty acid hydroperoxide lyase (CYP74B), prostacyclin synthase (CYP8; ) and thromboxane synthase (CYP5; ) are examples of P450 enzymes that do not require a reductase or molecular oxygen for their catalytic activity. Substrates for all these enzymes are fatty acid derivatives containing partially reduced dioxygen (either hydroperoxy or epidioxy groups).

References

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External links

Directory of P450-containing Systems

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