Cytochrome P450; 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 catalyze regiospecific and stereospecific oxidation of non-activated hydrocarbons at physiological temperatures.

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gi 1488192520  47 PKPSPFIGNLTFFRQG--FWESQMELRKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMP 112
Cdd:pfam00067   4 PPPLPLFGNLLQLGRKgnLHSVFTKLQKKYGPIFRLYLGPKPVVVLSGPEAVKEVLIKKGEEFSGRPD 71

cytochrome P450 family 3, subfamily A and similar cytochrome P450s; This family includes vertebrate CYP3A subfamily enzymes and CYP5a1, and similar proteins. CYP5A1, also called thromboxane-A synthase, converts prostaglandin H2 into thromboxane A2, a biologically active metabolite of arachidonic acid. CYP3A enzymes are drug-metabolizing enzymes embedded in the endoplasmic reticulum, where they can catalyze a wide variety of biochemical reactions including hydroxylation, N-demethylation, O-dealkylation, S-oxidation, deamination, or epoxidation of substrates. The CYP3A-like family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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gi 1488192520  74 YGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMP 112
Cdd:cd11055     2 YGKVFGLYFGTIPVIVVSDPEMIKEILVKEFSNFTNRPL 40

cytochrome P450; Provisional

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gi 1488192520  34 SAFSRLEKLGLRHPKPSPFIGNLTFFRQGFWESQMELRKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRmPQ 113
Cdd:PTZ00404   21 KKYKKIHKNELKGPIPIPILGNLHQLGNLPHRDLTKMSKKYGGIFRIWFADLYTVVLSDPILIREMFVDNFDNFSDR-PK 99

                          90
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gi 1488192520 114 SimPNSRHHVASRG 127
Cdd:PTZ00404  100 I--PSIKHGTFYHG 111

cytochrome P450 family 3, subfamily A; The cytochrome P450 3A (CYP3A) subfamily, the most abundant CYP subfamily in the liver, consists of drug-metabolizing enzymes. In humans, there are at least four isoforms: CYP3A4, 3A5, 3A7, and 3A3. CYP3A enzymes are embedded in the endoplasmic reticulum, where they can catalyze a wide variety of biochemical reactions including hydroxylation, N-demethylation, O-dealkylation, S-oxidation, deamination, or epoxidation of substrates. They oxidize a variety of structurally unrelated compounds including steroids, fatty acids, and xenobiotics. The CYP3A subfamily belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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gi 1488192520  74 YGPLCGYYLGRRMFIVISEPDMIKQVLV-ENFSNFTNRMP 112
Cdd:cd20650     2 YGKVWGIYDGRQPVLAITDPDMIKTVLVkECYSVFTNRRP 41

cytochrome P450 family 132 and similar cytochrome P450s; This subfamily is composed of Mycobacterium tuberculosis cytochrome P450 132 (CYP132) and similar proteins. The function of CYP132 is as yet unknown. CYP132 belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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gi 1488192520  75 GPLCGYYLGRRMFIVISEPDMIKQVLVENFSNF 107
Cdd:cd20620     1 GDVVRLRLGPRRVYLVTHPDHIQHVLVTNARNY 33

ferulate 5-hydroxylase

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1488192520  47 PKPSPFIGNLTFFRQGFWESQMELRKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNR 110
Cdd:PLN02183   41 PKGLPIIGNMLMMDQLTHRGLANLAKQYGGLFHMRMGYLHMVAVSSPEVARQVLQVQDSVFSNR 104

cytochrome P450 families 77 and 89, and similar cytochrome P450s; This group includes cytochrome P450 families 73 (CYP77) and 89 (CYP89), which are sister families that share a common ancestor. CYP89, present only in angiosperms, is younger than CYP77, which is already found in lycopods; thus, CYP89 may have evolved from CYP77 after duplication and divergence. Also included in this group is ent-kaurene oxidase, called CYP701A3 in Arabidopsis thaliana and CYP701B1 in Physcomitrella patens, that catalyzes the oxidation of ent-kaurene to form ent-kaurenoic acid. CYP701A3 is sensitive to inhibitor uniconazole-P while CYP701B1 is not. This CYP77/89 group belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1488192520  74 YGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNR---MPQSIMPNSRHH---VASRG-MWPGGRR--LACYLHPFRM 144
Cdd:cd11075     2 YGPIFTLRMGSRPLIVVASRELAHEALVQKGSSFASRppaNPLRVLFSSNKHmvnSSPYGpLWRTLRRnlVSEVLSPSRL 81

                  ..
gi 1488192520 145 AE 146
Cdd:cd11075    82 KQ 83

cytochrome P450 family 76 and similar cytochrome P450s; Characterized members of the plant cytochrome P450 family 76 (CYP76 or Cyp76) include: Catharanthus roseus CYP76B6, a multifunctional enzyme catalyzing two sequential oxidation steps leading to the formation of 8-oxogeraniol from geraniol; the Brassicaceae-specific CYP76C subfamily of enzymes that are involved in the metabolism of monoterpenols and phenylurea herbicides; and two P450s from Lamiaceae, CYP76AH and CYP76AK, that are involved in the oxidation of abietane diterpenes. CYP76AH produces ferruginol and 11-hydroxyferruginol, while CYP76AK catalyzes oxidations at the C20 position. Also included in this group is Berberis stolonifera Cyp80, also called berbamunine synthase or (S)-N-methylcoclaurine oxidase [C-O phenol-coupling], that catalyzes the phenol oxidation of N-methylcoclaurine to form the bisbenzylisoquinoline alkaloid berbamunine. The CYP76-like family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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gi 1488192520  71 RKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMPQSIMPNSRHHVAS 125
Cdd:cd11073     1 AKKYGPIMSLKLGSKTTVVVSSPEAAREVLKTHDRVLSGRDVPDAVRALGHHKSS 55

Plant cytochrome P450s, clan CYP72; CYPs have been classified into families and subfamilies based on homology and phylogenetic criteria; family membership is defined as 40% amino acid sequence identity or higher. The plant CYPs have also been classified according to clans; land plants have 11 clans that form two groups: single-family clans (CYP51, CYP74, CYP97, CYP710, CYP711, CYP727, CYP746) and multi-family clans (CYP71, CYP72, CYP85, CYP86). The CYP72 clan is associated with the metabolism of a diversity of fairly hydrophobic compounds including fatty acids and isoprenoids, with the catabolism of hormones (brassinosteroids and gibberellin, GA) and with the biosynthesis of cytokinins. This clan includes: CYP734 enzymes that are involved in brassinosteroid (BRs) catabolism and regulation of BRs homeostasis; CYP714 enzymes that are involved in the biosynthesis of gibberellins (GAs) and the mechanism to control their bioactive endogenous levels; and CYP72 family enzymes, among others. The CYP72 clan belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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gi 1488192520  71 RKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMPQ 113
Cdd:cd11052     8 IKQYGKNFLYWYGTDPRLYVTEPELIKELLSKKEGYFGKSPLQ 50

cytochrome P450 family 714; Cytochrome P450 family 714 (CYP714) belongs to the plant CYP72 clan, which is generally associated with the metabolism of a diversity of fairly hydrophobic compounds including fatty acids and isoprenoids, with the catabolism of hormones (brassinosteroids and gibberellin, GA) and with the biosynthesis of cytokinins. CYP714 enzymes are involved in the biosynthesis of gibberellins (GAs) and the mechanism to control their bioactive endogenous levels. They contribute to the production of diverse GA compounds through various oxidations of C and D rings in both monocots and eudicots. CYP714B1 and CYP714B2 encode the enzyme GA 13-oxidase, which is required for GA1 biosynthesis, while CYP714D1 encodes GA 16a,17-epoxidase, which inactivates the non-13-hydroxy GAs in rice. Arabidopsis CYP714A1 is an inactivation enzyme that catalyzes the conversion of GA12 to 16-carboxylated GA12 (16-carboxy-16beta,17-dihydro GA12). CYP714 belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

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gi 1488192520  71 RKLYGPLCGYYLGRRMFIVISEPDMIKQV 99
Cdd:cd20640     8 RKQYGPIFTYSTGNKQFLYVSRPEMVKEI 36