| Root |
Created: 1 November 1996
| Haem type | Haem iron coordination | Axial iron ligand(s) | Formal iron oxidation/spin states |
|---|---|---|---|
 |
 |
 Cys;
(H2O or OH¯) |
FeII (S=2);
FeIII (S=5/2) |
|
Cys;
O2, CO, NO or other ligand |
FeII (S=0);
FeIII (S=1/2) |
|
Cys;
O (O·) |
FeIV (S=1) |
P450 enzymes (P450s), also known as cytochromes P450, constitute a superfamily of haem-thiolate proteins [1], widely distributed in bacteria, fungi, plants and animals. The enzymes are involved in metabolism of a plethora of both exogenous and endogenous compounds [2]. Usually, they act as terminal oxidases in multicomponent electron transfer chains, called P450containing monooxygenase systems.
P450containing monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial (I), and microsomal (II). Alternatively, P450containing systems can be classified according to the number of their protein components [3]:
| Class | Number of protein components | Example of relevant electron transport chain | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I | Human mitochondrial |
| |||||||||||||||
| Pseudomonas putida camphor hydroxylase |
|
||||||||||||||||
| Pseudomonas sp. terpineol hydroxylase |
|
||||||||||||||||
| II | Human microsomal steroid 21hydroxylase |
|
|||||||||||||||
| Bacillus megaterium fatty acid monooxygenase |
|
||||||||||||||||
The most common reaction catalysed by P450 enzymes is a monooxygenase reaction,
i.e. insertion of one atom of oxygen into substrate while the other oxygen
atom is reduced to water:
Most P450 enzymes follow the reaction cycle
[4]:
The cycle is initiated by substrate (RH) binding to the native, predominantly
lowspin, hexacoordinate, ferric form I, converting it to the
highspin, pentacoordinate ferric complex II. Oneelectron
reduction of II yields the highspin, pentacoordinate ferrous
complex III. Complex III subsequently binds dioxygen
(O2) to form a `semistable' lowspin, hexacoordinate
ferrous-O2 adduct IV. Species I-IV of the P450
cycle and the lowspin, hexacoordinate ferrous-CO inhibitor complex
V have been isolated and well characterised. It is hypothesised that
such species as a lowspin, ferric peroxycomplex VI, and oxyferryl
(FeIV=O) intermediate VII, are further formed. Oxygen
atom transfer from VII to the substrate yields oxidised product (ROH)
and regenerates state I.
In the presence of external oxygenation agents, such as peracids, the complex
III may directly yield state VII via a `shunt' pathway.
Species I, II and VII are neutral, while the overall
charge of species III, IV and V is -1 and of species
VI is -2 [4].
The current P450 nomenclature, based on divergent evolution of the P450
superfamily, was proposed and developed by Nebert and coworkers
[5].
On the basis of sequence similarity, all P450s can be categorised into two
main groups, the socalled B (`bacterial') and E
(`eukaryotic') classes [6]. P450 proteins of
prokaryotic threecomponent systems and fungal P450nor (CYP55)
[7] belong to the Bclass; all
other known P450s from distinct systems, including bacterial
P450BM3 (CYP102) [8],
are of the Eclass. The data suggest that divergence of the P450
superfamily into B and Eclasses, and further divergence into stable
P450 groups within the Eclass, must be very ancient and had occurred
before the appearance of eukaryotes [6].
The 3D structures of several P450s have been reported:
P450cam [9],
the P450 domain of P450BM3
[10], P450terp
[11] and P450eryF
[12]. The P450 molecule is an
ROH + H2O
/ß protein, shaped like a
triangular prism (see Figure 3CPP a);
the overall structure has been described as being divided into
rich (`right side') and
ßrich (`left side') domains
[9-12].
However, this terminology is inappropriate, since the
and ßrich `domains'
comprise discontinuous assemblies of secondary structure segments and do not
constitute independent folding units. Although the sequence identity between
any two P450s with known 3D structure reaches only 20% or less, the
overall topology of the proteins is similar, with some differences in the
orientations of various helices. The most dramatic variations between P450
structures are found in regions responsible for substrate binding and access.
| ENZYME | LIGAND | BRENDA | UMBBD | Official name | Alternative name(s) | P450 family |
|---|---|---|---|---|---|---|
| 1.1.3.34 | 1.1.3.34 | Berbamunine synthase | (S)NMethylcoclaurine oxidase (C-O phenolcoupling) | CYP80 | ||
| 1.14.13.11 | 1.14.13.11 | 1.14.13.11 | transCinnamate 4monooxygenase | Cinnamic acid 4hydroxylase; cinnamate 4hydroxylase | CYP73 | |
| 1.14.13.12 | 1.14.13.12 | 1.14.13.12 | Benzoate 4monooxygenase | Benzoate parahydroxylase | CYP53 | |
| 1.14.13.13 | 1.14.13.13 | 1.14.13.13 | Calcidiol 1monooxygenase | 25hydroxycholecalciferol 1hydroxylase;
25hydroxycholecalciferol 1monooxygenase;
25hydroxyvitamin D3
1hydroxylase |
CYP27 | |
| 1.14.13.15 | 1.14.13.15 | 1.14.13.15 | Cholestanetriol 26monooxygenase | 5ßCholestane3,7,12triol hydroxylase;
cholestanetriol 26hydroxylase |
CYP27 | |
| 1.14.13.17 | 1.14.13.17 | 1.14.13.17 | Cholesterol 7monooxygenase |
Cholesterol 7hydroxylase |
CYP7 | |
| 1.14.13.21 | 1.14.13.21 | 1.14.13.21 | Flavonoid 3'monooxygenase | Flavonoid 3'hydroxylase | CYP75 | |
| 1.14.13.30 | 1.14.13.30 | 1.14.13.30 | LeukotrieneB4 20monooxygenase | LeukotrieneB4  hydroxylase;
leukotrieneB4 20hydroxylase |
CYP4F | |
| 1.14.13.41 | 1.14.13.41 | 1.14.13.41 | Tyrosine Nmonooxygenase | Tyrosine Nhydroxylase | CYP79 | |
| 1.14.13.52 | 1.14.13.52 | 1.14.13.52 | Isoflavone 3'hydroxylase | |||
| 1.14.13.53 | 1.14.13.53 | 1.14.13.53 | Isoflavone 2'hydroxylase | |||
| 1.14.13.- | 1.14.13.- | 1.14.13.- | e0201 | 4Nitrophenol 4monooxygenase | 4Nitrophenol monooxygenase; pnitrophenol hydroxylase | CYP2E1 |
| 1.14.14.1 | 1.14.14.1 | 1.14.14.1 | Unspecific monooxygenase | Aryl hydrocarbon hydroxylase; microsomal monooxygenase; xenobiotic monooxygenase | Multiple | |
| 1.14.15.1 | 1.14.15.1 | 1.14.15.1 | Camphor 5monooxygenase | Camphor 5exomethylene hydroxylase; cytochrome P450cam | CYP101 | |
| 1.14.15.3 | 1.14.15.3 | 1.14.15.3 | e0022 | Alkane 1monooxygenase | Alkane 1hydroxylase;
lauric acid hydroxylase;
hydroxylase;
fatty acid hydroxylase;
|
CYP4A |
| 1.14.15.4 | 1.14.15.4 | 1.14.15.4 | Steroid 11ßmonooxygenase | Steroid 11ßhydroxylase; steroid 11ß/18hydroxylase | CYP11B | |
| 1.14.15.5 | 1.14.15.5 | 1.14.15.5 | Corticosterone 18monooxygenase | Corticosterone 18hydroxylase; corticosterone methyloxidase | CYP11B | |
| 1.14.15.6 | 1.14.15.6 | 1.14.15.6 | Cholesterol monooxygenase (side chain cleavage) | Cholesterol desmolase; cholesterol side chain cleavage enzyme | CYP11A | |
| 1.14.15.- | 1.14.15.- | 1.14.15.- | e0090 | Atrazine monooxygenase | ||
| 1.14.15.- | 1.14.15.- | 1.14.15.- | e0094 | Deisopropylatrazine monooxygenase | ||
| 1.14.15.- | 1.14.15.- | 1.14.15.- | e0098 | Deethylatrazine monooxygenase | ||
| 1.14.99.9 | 1.14.99.9 | 1.14.99.9 | Steroid 17monooxygenase |
Steroid 17hydroxylase;
steroid 17hydroxylase/17,20 lyase |
CYP17 | |
| 1.14.99.10 | 1.14.99.10 | 1.14.99.10 | Steroid 21monooxygenase | Steroid 21hydroxylase | CYP21 | |
| 1.14.99.22 | 1.14.99.22 | 1.14.99.22 | Ecdysone 20monooxygenase | |||
| 1.14.99.28 | 1.14.99.28 | 1.14.99.28 | Linalool 8monooxygenase | CYP111 | ||
| 4.2.1.92 | 4.2.1.92 | 4.2.1.92 | Hydroperoxide dehydratase | Hydroperoxide isomerase; allene oxide synthase | CYP74 | |
| 5.3.99.4 | 5.3.99.4 | 5.3.99.4 | ProstaglandinI synthase | Prostacyclin synthase | CYP8 | |
| 5.3.99.5 | 5.3.99.5 | 5.3.99.5 | ThromboxaneA synthase | Thromboxane synthase; thromboxane synthetase | CYP5 | |
| PRINTS ID | PRINTS AC | PROSITE/BLOCKS ID | PROSITE AC | BLOCKS AC |
|---|---|---|---|---|
| BP450 | PR00359 | CYTOCHROME_P450 | PS00086 | BL00086 |
| EP450I | PR00463 | |||
| EP450II | PR00464 | |||
| EP450IV | PR00465 | |||
| MITP450 | PR00408 | |||
| P450 | PR00385 |
| Protein Superfamily | Pfam | LPFC 3D alignment | MolMovDB |
|---|---|---|---|
|
00027;
cytochrome P450
04333; P450 bifunctional enzyme |
| PDB | scop | BSM | RELI Base | Header | 
¹ |
|---|---|---|---|---|---|
| 1akd | 1akd | 1akd | 1akd | P450cam (complex with 1Scamphor and K+); Pseudomonas putida | |
| 1bu7 | 1bu7 | 1bu7 | P450BM3 (haemoprotein domain) (100 K) (complex with ethylene glycol); Bacillus megaterium (recombinant form expressed in Escherichia coli) | ||
| 1cp4 | 1cp4 | 1cp4 | 1cp4 | P450cam (complex with phenyl radical); Pseudomonas putida | |
| 1cpt | 1cpt | 1cpt | 1cpt | P450terp; Pseudomonas sp. (recombinant form expressed in Escherichia coli) | MS5AW4 |
| 1fag | 1fag | 1fag | 1fag | P450BM3 (haemoprotein domain) (complex with palmitoleic acid); Bacillus megaterium 14581 (recombinant form expressed in Escherichia coli) | |
| 1fah | 1fah | 1fah | 1fah | P450BM3 (haemoprotein domain) (T268A mutant); Bacillus megaterium 14581 (recombinant form expressed in Escherichia coli) | |
| 1noo | 1noo | 1noo | 1noo | P450cam (complex with 5exohydroxycamphor; Pseudomonas putida | |
| 1oxa | 1oxa | 1oxa | 1oxa | P450eryF (complex with 6deoxyerythronolide B); Saccarapolyspora erythraea | |
| 1pha | 1pha | 1pha | 1pha | P450cam [complex with 1(Nimidazolyl)2hydroxy2(2,3dichlorophenyl)octane]; Pseudomonas putida | |
| 1phb | 1phb | 1phb | 1phb | P450cam [complex with 1(Nimidazolyl)2hydroxy2(2,3dichlorophenyl)octane]; Pseudomonas putida | |
| 1phc | 1phc | 1phc | 1phc | P450cam; Pseudomonas putida | |
| 1phd | 1phd | 1phd | 1phd | P450cam (complex with 2phenylimidazole); Pseudomonas putida | |
| 1phe | 1phe | 1phe | 1phe | P450cam (complex with 2phenylimidazole and sulphate); Pseudomonas putida | |
| 1phf | 1phf | 1phf | 1phf | P450cam (complex with 2phenylimidazole); Pseudomonas putida | |
| 1phg | 1phg | 1phg | 1phg | P450cam (complex with metyrapone); Pseudomonas putida | |
| 1rom | 1rom | 1rom | 1rom | P450nor, nitric oxide reductase; Fusarium oxysporum | |
| 2bmh | 2bmh | 2bmh | 2bmh | P450BM3 (haemoprotein domain); Bacillus megaterium 14581 (recombinant form expressed in Escherichia coli) | MMS94082 |
| 2cp4 | 2cp4 | 2cp4 | 2cp4 | P450cam (complex with camphor) (T252A mutant); Pseudomonas putida | |
| 2cpp | 2cpp | 2cpp | 2cpp | P450cam (complex with camphor); Pseudomonas putida | |
| 2hpd | 2hpd | 2hpd | 2hpd | P450BM3 (haemoprotein domain); Bacillus megaterium (recombinant form expressed in Escherichia coli) | |
| 2rom | 2rom | 2rom | 2rom | P450nor, nitric oxide reductase (complex with CO); Fusarium oxysporum | |
| 3cp4 | 3cp4 | 3cp4 | 3cp4 | P450cam (complex with adamantane); Pseudomonas putida (recombinant form expressed in Escherichia coli) | |
| 3cpp | 3cpp | 3cpp | 3cpp | P450cam (complex with CO and reduced camphor); Pseudomonas putida | |
| 4cp4 | 4cp4 | 4cp4 | 4cp4 | P450cam (complex with camphor); Pseudomonas putida | |
| 4cpp | 4cpp | 4cpp | 4cpp | P450cam (complex with adamantane); Pseudomonas putida | |
| 5cp4 | 5cp4 | P450cam (complex with camphor, glycerol and K+) (100 K); Pseudomonas putida (recombinant form expressed in Escherichia coli) | |||
| 5cpp | 5cpp | 5cpp | 5cpp | P450cam (complex with adamantanone); Pseudomonas putida | |
| 6cp4 | 6cp4 | P450cam (complex with camphor, glycerol and K+) (D251N mutant) (100 K); Pseudomonas putida (recombinant form expressed in Escherichia coli) | |||
| 6cpp | 6cpp | 6cpp | 6cpp | P450cam (complex with camphane); Pseudomonas putida | |
| 7cpp | 7cpp | 7cpp | 7cpp | P450cam (complex with norcamphor); Pseudomonas putida | |
| 8cpp | 8cpp | 8cpp | 8cpp | P450cam (complex with thiocamphor); Pseudomonas putida |
¹ Macromolecular Structures abstract.
Full text is available to BioMedNet
Members
References
| Bibliography on structural studies of P450s |
|
| Reviews on P450s |
| Directory of P450containing Systems |
