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P450-containing systems



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

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Contents

Overview

P450 enzymes usually act as terminal oxidase in multicomponent electron-transfer chains, called P450-containing monooxygenase systems, although self-sufficient non-monooxygenase P450s are also described. All known P450-containing monooxygenase systems share common structural and functional domain architecture. Apart from P450 itself, these systems contain one or more fundamental redox domains: FAD-containing flavoprotein or domain, FMN domain, ferredoxin and cytochrome b5. These ubiquitous redox domains, in various combinations, are widely distributed in biological systems. FMN domain, ferredoxin or cytochrome b5 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).

    NADH
    putidaredoxin reductase
    putidaredoxin
    CYP101
    O2
    NADH
    terpredoxin reductase
    terpredoxin
    CYP108
    O2
    NADH
    rhodocoxin reductase
    rhodocoxin
    CYP116
    O2

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

    NAD(P)H
    FAD
    Fe2S2
    P450
    O2

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; EC 1.6.2.4). 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:

    NADPH
    FAD
    FMN
    P450
    O2

CBR/b5/P450 systems

The ubiquitous electron-transport protein cytochrome b5 can serve as an effector (activator or inhibitor) of P450s. It was hypothesized that cytochrome b5 is involved in the transfer of the second electron to P450, either from CPR or NADH:cytochrome b5 reductase (CBR; EC 1.6.2.2):

    NADPH
    CPR
    cyt b5
    P450
    O2
    NADH
    CBR
    cyt b5
    P450
    O2

The ability of the CBR/cytochrome b5 system to support P450 catalysis has been demonstrated in vitro using purified CBR and cytochrome b5 from Saccharomyces cerevisiae and CYP51 enzyme from Candida albicans. In this system, both the first and second electrons are donated by CBR.

    NAD(P)H
    FAD
    b5
    P450
    O2

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:

    NADH
    FMN
    Fe2S2
    P450
    O2

P450-only systems

Nitric oxide reductase (P450nor) is a P450 enzyme involved in denitrification in several fungal species. The best characterized P450nor is CYP55 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:

    NAD(P)H
    P450
    NO·

Fatty acid β-hydroxylase P450BSβ from Bacillus subtilis (CYP152A1) and fatty acid α-hydroxylase P450SPα 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; EC 4.2.1.92), fatty acid hydroperoxide lyase (CYP74B), prostacyclin synthase (CYP8; EC 5.3.99.4) and thromboxane synthase (CYP5; EC 5.3.99.5) are examples of P450 enzymes which 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

  • Degtyarenko, K.N. and Kulikova, T.A. (2001). "Evolution of bioinorganic motifs in P450-containing systems". Biochem. Soc. Trans. 29: 139–147. PMID 11356142.
  • Hanukoglu, I. (1996). "Electron transfer proteins of cytochrome P450 systems". Adv. Mol. Cell Biol. 14: 29–55.
  • McLean, K.J., Sabri, M., Marshall, K.R., Lawson, R.J., Lewis, D.G., Clift, D., Balding, P.R., Dunford, A.J., Warman, A.J., McVey, J.P., Quinn, A.-M., Sutcliffe, M.J., Scrutton, N.S. and Munro, A.W. (2005). "Biodiversity of cytochrome P450 redox systems". Biochem. Soc. Trans. 33: 796–801. PMID 16042601.
  • Ohta, D. and Mizutani, M. (2004). "Redundancy or flexibility: molecular diversity of the electron transfer components for P450 monooxygenases in higher plants". Front. Biosci. 9: 1587–1597. PMID 14977570.
  • Roberts, G.A., Çelik, A., Hunter, D.J.B., Ost, T.W.B., White, J.H., Chapman, S.K., Turner, N.J. and Flitsch, S.L. (2003). "A self-sufficient cytochrome P450 with a primary structural organisation that includes a flavin domain and a [2Fe-2S] redox center". J. Biol. Chem. 278: 48914–48920. PMID 14514666.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "P450-containing_systems". A list of authors is available in Wikipedia.
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