Summary: Cytochrome P450
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Cytochrome P450 Edit Wikipedia article
Cytochrome P450 is a generic term used to describe a class of enzymes which catalyze the oxidative metabolism of a variety of compounds. In most animals, including humans, hepatic cytochrome P450s are the most widely studied of the P450 enzymes.
The term cytochrome P450 refers to the fact that these enzymes have a light absorbtion peak at 450 nm when bound to Carbon Monoxide.
Genes for the P450 enzymes are labelled with the abbreviation CYP, followed by an Arabic number indicating the gene family, a capital letter indicating the subfamily, and an Arabic number for the individual gene. For example, CYP2E1 is the designation given to the gene responsible for ethanol metabolism.
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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Cytochrome P450s are haem-thiolate proteins  involved in the oxidative degradation of various compounds. They are particularly well known for their role in the degradation of environmental toxins and mutagens. They can be divided into 4 classes, according to the method by which electrons from NAD(P)H are delivered to the catalytic site. Sequence conservation is relatively low within the family - there are only 3 absolutely conserved residues - but their general topography and structural fold are highly conserved. The conserved core is composed of a coil termed the 'meander', a four-helix bundle, helices J and K, and two sets of beta-sheets. These constitute the haem-binding loop (with an absolutely conserved cysteine that serves as the 5th ligand for the haem iron), the proton-transfer groove and the absolutely conserved EXXR motif in helix K. While prokaryotic P450s are soluble proteins, most eukaryotic P450s are associated with microsomal membranes. their general enzymatic function is to catalyse regiospecific and stereospecific oxidation of non-activated hydrocarbons at physiological temperatures .
Graham-Lorence S, Amarneh B, White RE, Peterson JA, Simpson ER; , Protein Sci 1995;4:1065-1080.: A three-dimensional model of aromatase cytochrome P450. PUBMED:7549871 EPMC:7549871
Degtyarenko KN, Archakov AI; , FEBS Lett 1993;332:1-8.: Molecular evolution of P450 superfamily and P450-containing monooxygenase systems. PUBMED:8405421 EPMC:8405421
Nelson DR, Kamataki T, Waxman DJ, Guengerich FP, Estabrook RW, Feyereisen R, Gonzalez FJ, Coon MJ, Gunsalus IC, Gotoh O, et al; , DNA Cell Biol 1993;12:1-51.: The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. PUBMED:7678494 EPMC:7678494
Guengerich FP; , J Biol Chem 1991;266:10019-10022.: Reactions and significance of cytochrome P-450 enzymes. PUBMED:2037557 EPMC:2037557
Nebert DW, Gonzalez FJ; , Annu Rev Biochem 1987;56:945-993.: P450 genes: structure, evolution, and regulation. PUBMED:3304150 EPMC:3304150
Werck-Reichhart D, Feyereisen R; , Genome Biol 2000;1:REVIEWS3003.: Cytochromes P450: a success story. PUBMED:11178272 EPMC:11178272
External database links
|PRINTS:||PR00385 PR00359 PR00408 PR00463 PR00464 PR00465|
This tab holds annotation information from the InterPro database.
InterPro entry IPR001128
Cytochrome P450 enzymes are a superfamily of haem-containing mono-oxygenases that are found in all kingdoms of life, and which show extraordinary diversity in their reaction chemistry. In mammals, these proteins are found primarily in microsomes of hepatocytes and other cell types, where they oxidise steroids, fatty acids and xenobiotics, and are important for the detoxification and clearance of various compounds, as well as for hormone synthesis and breakdown, cholesterol synthesis and vitamin D metabolism. In plants, these proteins are important for the biosynthesis of several compounds such as hormones, defensive compounds and fatty acids. In bacteria, they are important for several metabolic processes, such as the biosynthesis of antibiotic erythromycin in Saccharopolyspora erythraea (Streptomyces erythraeus).
Cytochrome P450 enzymes use haem to oxidise their substrates, using protons derived from NADH or NADPH to split the oxygen so a single atom can be added to a substrate. They also require electrons, which they receive from a variety of redox partners. In certain cases, cytochrome P450 can be fused to its redox partner to produce a bi-functional protein, such as with P450BM-3 from Bacillus megaterium [ PUBMED:17023115 ], which has haem and flavin domains.
Organisms produce many different cytochrome P450 enzymes (at least 58 in humans), which together with alternative splicing can provide a wide array of enzymes with different substrate and tissue specificities. Individual cytochrome P450 proteins follow the nomenclature: CYP, followed by a number (family), then a letter (subfamily), and another number (protein); e.g. CYP3A4 is the fourth protein in family 3, subfamily A. In general, family members should share >40% identity, while subfamily members should share >55% identity.
Cytochrome P450 proteins can also be grouped by two different schemes. One scheme was based on a taxonomic split: class I (prokaryotic/mitochondrial) and class II (eukaryotic microsomes). The other scheme was based on the number of components in the system: class B (3-components) and class E (2-components). These classes merge to a certain degree. Most prokaryotes and mitochondria (and fungal CYP55) have 3-component systems (class I/class B) - a FAD-containing flavoprotein (NAD(P)H-dependent reductase), an iron-sulphur protein and P450. Most eukaryotic microsomes have 2-component systems (class II/class E) - NADPH:P450 reductase (FAD and FMN-containing flavoprotein) and P450. There are exceptions to this scheme, such as 1-component systems that resemble class E enzymes [ PUBMED:16042601 , PUBMED:15128046 , PUBMED:8637843 ]. The class E enzymes can be further subdivided into five sequence clusters, groups I-V, each of which may contain more than one cytochrome P450 family (eg, CYP1 and CYP2 are both found in group I). The divergence of the cytochrome P450 superfamily into B- and E-classes, and further divergence into stable clusters within the E-class, appears to be very ancient, occurring before the appearance of eukaryotes.
This family also includes germacrene A hydroxylase (GAO1; EC ) from plants such as lettuce (Lactuca sativa). GAO1 is required for the biosynthesis of germacrene-derived sesquiterpene lactones, which are characteristic natural products in members of the Asteraceae [ PUBMED:20351109 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||heme binding (GO:0020037)|
|oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705)|
|iron ion binding (GO:0005506)|
|monooxygenase activity (GO:0004497)|
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||Overington and HMM_iterative_training|
|Number in seed:||50|
|Number in full:||213489|
|Average length of the domain:||340.7 aa|
|Average identity of full alignment:||17 %|
|Average coverage of the sequence by the domain:||78.98 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||25|
|Download:||download the raw HMM for this family|
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the p450 domain has been found. There are 2175 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.