P450-containing 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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The sterol demethylase system from Mycobacterium tuberculosis contains flavoprotein reductase A (FprA), bacterial-type Fe₃S₄ ferredoxin and CYP51 hemoprotein.{{cite journal |author1 =McLean, K.J. |author2 =Warman, A.J. |author3 =Seward, H.E. |author4 =Marshall, K.R. |author5 =Girvan, H.M. |author6 =Cheesman, M.R. |author7 =Waterman, M.R. |author8 =Munro, A.W. | title=Biophysical characterization of the sterol demethylase P450 from Mycobacterium tuberculosis, its cognate ferredoxin, and their interactions | journal=Biochemistry | year=2006 | volume=45 |issue=27 | pages=8427–8443 | pmid=16819841 | doi=10.1021/bi0601609}}

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Eukaryotic microsomal P450 enzymes and some bacterial P450s receive electrons from a FAD- and FMN-containing enzyme known as cytochrome P450 reductase (CPR; {{EC number|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:

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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 from NADH:cytochrome b₅ reductase (CBR; {{EC number|1.6.2.2}}):

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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.

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An unusual one-component P450 system was originally found in Rhodococcus sp. NCIMB 9784 ([http://uniprot.org/entry/Q8KU27 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.{{cite journal |author1 =Roberts, G.A. |author2 =Çelik, A. |author3 =Hunter, D.J.B. |author4 =Ost, T.W.B. |author5 =White, J.H. |author6 =Chapman, S.K. |author7 =Turner, N.J. |author8 =Flitsch, S.L. | title=A self-sufficient cytochrome P450 with a primary structural organisation that includes a flavin domain and a [2Fe-2S] redox center | journal=J. Biol. Chem. | year=2003 | volume=278 |issue =49 | pages=48914–48920 | pmid=14514666 | doi=10.1074/jbc.M309630200|url =http://espace.library.uq.edu.au/view/UQ:414787/UQ414787_OA.pdf |doi-access =free }} Similar systems have been identified in the heavy-metal-tolerant bacterium Ralstonia metallidurans ([http://uniprot.org/entry/Q3RV41 CYP116A1]) and in several species of Burkolderia.

The general scheme of electron flow in this system appears to be:

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Nitric oxide reductase (P450nor) is a P450 enzyme involved in denitrification in several fungal species. The best-characterized P450nor is [http://uniprot.org/entry/P23295 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 ([http://uniprot.org/entry/O31440 CYP152A1]) and fatty acid α-hydroxylase P450_SPα from Pseudomonas paucimobilis ([http://uniprot.org/entry/O24782 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 number|4.2.1.92}}), fatty acid hydroperoxide lyase (CYP74B), prostacyclin synthase (CYP8; {{EC number|5.3.99.4}}) and thromboxane synthase (CYP5; {{EC number|5.3.99.5}}) 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).

{{Reflist}}

• [https://web.archive.org/web/20080509142511/https://www.icgeb.org/~p450srv/ Directory of P450-containing Systems]

{{Multienzyme complexes}}

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