cytochrome P450 (CYP) superfamily; Cytochrome P450 (P450, CYP) is a large 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 with > 40% sequence identity are members of the same family. There are approximately 2250 CYP families: mammals, insects, plants, fungi, bacteria, and archaea have around 18, 208, 277, 805, 591, and 14 families, respectively. 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. Their monooxygenase activity relies on the reductive scission of molecular oxygen bound to the P450 heme iron, and the delivery of two electrons to the heme iron during the catalytic cycle. CYPs use a variety of redox partners, such as the eukaryotic diflavin enzyme NADPH-cytochrome P450 oxidoreductase and the bacterial/mitochondrial NAD(P)H-ferredoxin reductase and ferredoxin partners. Some CYPs are naturally linked to their redox partners and others have evolved to bypass requirements for redox partners, and instead react directly with hydrogen peroxide or NAD(P)H to facilitate oxidative or reductive catalysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  69 PRMCLLWIGPFPCLMLYSADLVEPIFSSTKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIF 148
Cdd:cd20660     1 GPIFRIWLGPKPIVVLYSAETVEVILSSSKHIDKSFEYDFLHPWLGTGLLTSTGEKWHSRRKMLTPTFHFKILEDFLDVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 149 NEQSKILIQKLCCLgVADEEVDVLSVITLCTLDIICETSMGKAIGAQLAENNEYVWAVHTINKLISKRTNNPLMWNSFIY 228
Cdd:cd20660    81 NEQSEILVKKLKKE-VGKEEFDIFPYITLCALDIICETAMGKSVNAQQNSDSEYVKAVYRMSELVQKRQKNPWLWPDFIY 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1254009998 229 NLTEDGRTHEKCLHILHDFTKKVIVERKEALQDS-----------DYKMEGRLAF 272
Cdd:cd20660   160 SLTPDGREHKKCLKILHGFTNKVIQERKAELQKSleeeeeddedaDIGKRKRLAF 214

cytochrome P450 family 4, subfamily V, and similar cytochrome P450s; This group is composed of vertebrate cytochrome P450 family 4, subfamily V (CYP4V) enzymes and similar proteins, including invertebrate subfamily C (CYP4C). Insect CYP4C enzymes may be involved in the metabolism of insect hormones and in the breakdown of synthetic insecticides. CYP4V2, the most characterized member of the CYP4V subfamily, is a selective omega-hydroxylase of saturated, medium-chain fatty acids, such as laurate, myristate and palmitate, with high catalytic efficiency toward myristate. Polymorphisms in the CYP4V2 gene cause Bietti's crystalline corneoretinal dystrophy (BCD), a recessive degenerative retinopathy that is characterized clinically by a progressive decline in central vision, night blindness, and constriction of the visual field. The CYP4V-like 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  69 PRMCLLWIGPFPCLMLYSADLVEPIFSSTKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIF 148
Cdd:cd20660     1 GPIFRIWLGPKPIVVLYSAETVEVILSSSKHIDKSFEYDFLHPWLGTGLLTSTGEKWHSRRKMLTPTFHFKILEDFLDVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 149 NEQSKILIQKLCCLgVADEEVDVLSVITLCTLDIICETSMGKAIGAQLAENNEYVWAVHTINKLISKRTNNPLMWNSFIY 228
Cdd:cd20660    81 NEQSEILVKKLKKE-VGKEEFDIFPYITLCALDIICETAMGKSVNAQQNSDSEYVKAVYRMSELVQKRQKNPWLWPDFIY 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1254009998 229 NLTEDGRTHEKCLHILHDFTKKVIVERKEALQDS-----------DYKMEGRLAF 272
Cdd:cd20660   160 SLTPDGREHKKCLKILHGFTNKVIQERKAELQKSleeeeeddedaDIGKRKRLAF 214

fatty acid omega-hydroxylase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998   7 AVLLASATVIAWLiykhLRMRQVLKHLNQPRSYPIVGHGL--ITKPDPegfMNQVIgMGYLYPDPRMCLlwigPFPCLML 84
Cdd:PLN03195   10 GVLFIALAVLSWI----FIHRWSQRNRKGPKSWPIIGAALeqLKNYDR---MHDWL-VEYLSKDRTVVV----KMPFTTY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  85 -YSADL--VEPIFSsTKHLN--KGFAY-VLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDF-LPIFNEQSKILIQ 157
Cdd:PLN03195   78 tYIADPvnVEHVLK-TNFANypKGEVYhSYMEVLLGDGIFNVDGELWRKQRKTASFEFASKNLRDFsTVVFREYSLKLSS 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 158 KLCCLGVADEEVDVLSVITLCTLDIICETSMGKAIGAqLAE---NNEYVWAVHTINKLISKRTNNPLmW--NSFIYNLTE 232
Cdd:PLN03195  157 ILSQASFANQVVDMQDLFMRMTLDSICKVGFGVEIGT-LSPslpENPFAQAFDTANIIVTLRFIDPL-WklKKFLNIGSE 234

                         250       260       270
                  ....*....|....*....|....*....|
gi 1254009998 233 dgRTHEKCLHILHDFTKKVIVERKEALQDS 262
Cdd:PLN03195  235 --ALLSKSIKVVDDFTYSVIRRRKAEMDEA 262

cytochrome P450 family 4, subfamily V, and similar cytochrome P450s; This group is composed of vertebrate cytochrome P450 family 4, subfamily V (CYP4V) enzymes and similar proteins, including invertebrate subfamily C (CYP4C). Insect CYP4C enzymes may be involved in the metabolism of insect hormones and in the breakdown of synthetic insecticides. CYP4V2, the most characterized member of the CYP4V subfamily, is a selective omega-hydroxylase of saturated, medium-chain fatty acids, such as laurate, myristate and palmitate, with high catalytic efficiency toward myristate. Polymorphisms in the CYP4V2 gene cause Bietti's crystalline corneoretinal dystrophy (BCD), a recessive degenerative retinopathy that is characterized clinically by a progressive decline in central vision, night blindness, and constriction of the visual field. The CYP4V-like 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  69 PRMCLLWIGPFPCLMLYSADLVEPIFSSTKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIF 148
Cdd:cd20660     1 GPIFRIWLGPKPIVVLYSAETVEVILSSSKHIDKSFEYDFLHPWLGTGLLTSTGEKWHSRRKMLTPTFHFKILEDFLDVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 149 NEQSKILIQKLCCLgVADEEVDVLSVITLCTLDIICETSMGKAIGAQLAENNEYVWAVHTINKLISKRTNNPLMWNSFIY 228
Cdd:cd20660    81 NEQSEILVKKLKKE-VGKEEFDIFPYITLCALDIICETAMGKSVNAQQNSDSEYVKAVYRMSELVQKRQKNPWLWPDFIY 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1254009998 229 NLTEDGRTHEKCLHILHDFTKKVIVERKEALQDS-----------DYKMEGRLAF 272
Cdd:cd20660   160 SLTPDGREHKKCLKILHGFTNKVIQERKAELQKSleeeeeddedaDIGKRKRLAF 214

cytochrome P450 family 4, subfamily V; Cytochrome P450 family 4, subfamily V, polypeptide 2 (CYP4V2) is the most characterized member of the CYP4V subfamily. It is a selective omega-hydroxylase of saturated, medium-chain fatty acids, such as laurate, myristate and palmitate, with high catalytic efficiency toward myristate. Polymorphisms in the CYP4V2 gene cause Bietti's crystalline corneoretinal dystrophy (BCD), a recessive degenerative retinopathy that is characterized clinically by a progressive decline in central vision, night blindness, and constriction of the visual field. The CYP4V 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  74 LWIGPFPCLMLYSADLVEPIFSSTKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQSK 153
Cdd:cd20680    17 LWIGPVPFVILYHAENVEVILSSSKHIDKSYLYKFLHPWLGTGLLTSTGEKWRSRRKMLTPTFHFTILSDFLEVMNEQSN 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 154 ILIQKLCCLgVADEEVDVLSVITLCTLDIICETSMGKAIGAQLAENNEYVWAVHTINKLISKRTNNPLMWNSFIYNLTED 233
Cdd:cd20680    97 ILVEKLEKH-VDGEAFNCFFDITLCALDIICETAMGKKIGAQSNKDSEYVQAVYRMSDIIQRRQKMPWLWLDLWYLMFKE 175

                         170       180
                  ....*....|....*....|....*..
gi 1254009998 234 GRTHEKCLHILHDFTKKVIVERKEALQ 260
Cdd:cd20680   176 GKEHNKNLKILHTFTDNVIAERAEEMK 202

cytochrome P450 family 313 and similar cytochrome P450s; This subfamily is composed of insect cytochrome P450s from families 313 (CYP313) and 318 (CYP318), and similar proteins. These proteins may be involved in the metabolism of insect hormones and in the breakdown of synthetic insecticides. Their specific function is yet unknown. They belong 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  69 PRMCLLWIGPFPCLMLYSADLVEPIFSSTKHLNKGFAYVLLepWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIF 148
Cdd:cd11057     1 GSPFRAWLGPRPFVITSDPEIVQVVLNSPHCLNKSFFYDFF--RLGRGLFSAPYPIWKLQRKALNPSFNPKILLSFLPIF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 149 NEQSKILIQKLCCLgVADEEVDVLSVITLCTLDIICETSMGKAIGAQLAENNEYVWAVHTINKLISKRTNNPLMWNSFIY 228
Cdd:cd11057    79 NEEAQKLVQRLDTY-VGGGEFDILPDLSRCTLEMICQTTLGSDVNDESDGNEEYLESYERLFELIAKRVLNPWLHPEFIY 157

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1254009998 229 NLTEDGRTHEKCLHILHDFTKKVIVERKEALQDSD 263
Cdd:cd11057   158 RLTGDYKEEQKARKILRAFSEKIIEKKLQEVELES 192

cytochrome P450 family 4, subfamily F; Cytochrome P450 family 4, subfamily F (CYP4F) enzymes are known for known for omega-hydroxylation of very long fatty acids (VLFA; C18-C26), leukotrienes, prostaglandins, and vitamins with long alkyl side chains. The CYP4F subfamily show diverse specificities among its members: CYP4F2 and CYP4F3 metabolize pro- and anti-inflammatory leukotrienes; CYP4F8 and CYP4F12 metabolize prostaglandins, endoperoxides and arachidonic acid; CYP4F11 and CYP4F12 metabolize VLFA and are unique in the CYP4F subfamily since they also hydroxylate xenobiotics such as benzphetamine, ethylmorphine, erythromycin, and ebastine. CYP4F 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  69 PRMCLLWIGPF-PCLMLYSADLVEPIF--SSTKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFL 145
Cdd:cd20679    12 PQGCLWWLGPFyPIIRLFHPDYIRPVLlaSAAVAPKDELFYGFLKPWLGDGLLLSSGDKWSRHRRLLTPAFHFNILKPYV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 146 PIFNEQSKILI---QKLCCLGVAdeEVDVLSVITLCTLDIICETSMGKAIGAQlAENNEYVWAVHTINKLISKRTNNPLM 222
Cdd:cd20679    92 KIFNQSTNIMHakwRRLASEGSA--RLDMFEHISLMTLDSLQKCVFSFDSNCQ-EKPSEYIAAILELSALVVKRQQQLLL 168

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1254009998 223 WNSFIYNLTEDGRTHEKCLHILHDFTKKVIVERKEALQD 261
Cdd:cd20679   169 HLDFLYYLTADGRRFRRACRLVHDFTDAVIQERRRTLPS 207

cytochrome P450 family 46, subfamily A, polypeptide 1, also called cholesterol 24-hydroxylase, and similar cytochrome P450s; CYP46A1 is also called cholesterol 24-hydroxylase (EC 1.14.14.25), CH24H, cholesterol 24-monooxygenase, or cholesterol 24S-hydroxylase. It catalyzes the conversion of cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. CYP46A1 is associated with high-order brain functions; increased expression improves cognition while a reduction leads to a poor cognitive performance. It also plays a role in the pathogenesis or progression of neurodegenerative disorders. CYP46A1 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  72 CLLWIGPFPCLMLYSADLVEPIFSSTKHLN-----KGFAYVLLEPWLGISILTSQ-KEQWRPKRKLLTPTFHYDILKDFL 145
Cdd:cd20613    15 FVFWILHRPIVVVSDPEAVKEVLITLNLPKpprvySRLAFLFGERFLGNGLVTEVdHEKWKKRRAILNPAFHRKYLKNLM 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 146 PIFNEQSKILIQKLccLGVAD--EEVDVLSVITLCTLDIICETSMGKAIGAQLAENNEYVWAVHTINKLISKRTNNPLMW 223
Cdd:cd20613    95 DEFNESADLLVEKL--SKKADgkTEVNMLDEFNRVTLDVIAKVAFGMDLNSIEDPDSPFPKAISLVLEGIQESFRNPLLK 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1254009998 224 -NSFIYNLTEDGRtheKCLHILHDFTKKVIVERKEALQDSDY 264
Cdd:cd20613   173 yNPSKRKYRREVR---EAIKFLRETGRECIEERLEALKRGEE 211

cytochrome P450 family/clan 97; 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). Members of the CYP97 clan include Arabidopsis thaliana cytochrome P450s 97A3 (CYP97A3), CYP97B3, and CYP97C1. CYP97A3 is also called protein LUTEIN DEFICIENT 5 (LUT5) and CYP97C1 is also called carotene epsilon-monooxygenase or protein LUTEIN DEFICIENT 1 (LUT1). These cytochromes function as beta- and epsilon-ring carotenoid hydroxylases and are involved in the biosynthesis of xanthophylls. CYP97 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 101 NKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQSKILIQKLCCLGVADEEVDVLSVITLCTL 180
Cdd:cd11046    45 KKGLLAEILEPIMGKGLIPADGEIWKKRRRALVPALHKDYLEMMVRVFGRCSERLMEKLDAAAETGESVDMEEEFSSLTL 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 181 DIICETSMGKAIGAqLAENNEYVWAVHT-INKLISKRTNNPLMWNSFIYNLTEDG-RTHEKCLHILHDFTKKVIVERKEA 258
Cdd:cd11046   125 DIIGLAVFNYDFGS-VTEESPVIKAVYLpLVEAEHRSVWEPPYWDIPAALFIVPRqRKFLRDLKLLNDTLDDLIRKRKEM 203

                         170
                  ....*....|.
gi 1254009998 259 LQDSDYKMEGR 269
Cdd:cd11046   204 RQEEDIELQQE 214

cytochrome P450 (CYP) superfamily; Cytochrome P450 (P450, CYP) is a large 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 with > 40% sequence identity are members of the same family. There are approximately 2250 CYP families: mammals, insects, plants, fungi, bacteria, and archaea have around 18, 208, 277, 805, 591, and 14 families, respectively. 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. Their monooxygenase activity relies on the reductive scission of molecular oxygen bound to the P450 heme iron, and the delivery of two electrons to the heme iron during the catalytic cycle. CYPs use a variety of redox partners, such as the eukaryotic diflavin enzyme NADPH-cytochrome P450 oxidoreductase and the bacterial/mitochondrial NAD(P)H-ferredoxin reductase and ferredoxin partners. Some CYPs are naturally linked to their redox partners and others have evolved to bypass requirements for redox partners, and instead react directly with hydrogen peroxide or NAD(P)H to facilitate oxidative or reductive catalysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  74 LWIGPFPCLMLYSADLVEPIFSSTKHLNKGFAYVL--LEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQ 151
Cdd:cd00302     6 VRLGGGPVVVVSDPELVREVLRDPRDFSSDAGPGLpaLGDFLGDGLLTLDGPEHRRLRRLLAPAFTPRALAALRPVIREI 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 152 SKILIQKLccLGVADEEVDVLSVITLCTLDIICETSMGKAIGAQLAennEYVWAVHTINKLISKRTNNPLmwnsfiynLT 231
Cdd:cd00302    86 ARELLDRL--AAGGEVGDDVADLAQPLALDVIARLLGGPDLGEDLE---ELAELLEALLKLLGPRLLRPL--------PS 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1254009998 232 EDGRTHEKCLHILHDFTKKVIVERKEALQDSDYKMEGRLA 271
Cdd:cd00302   153 PRLRRLRRARARLRDYLEELIARRRAEPADDLDLLLLADA 192

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  73 LLWIGPFPCLMLYSADLVEPIFS-STKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQ 151
Cdd:cd11052    16 LYWYGTDPRLYVTEPELIKELLSkKEGYFGKSPLQPGLKKLLGRGLVMSNGEKWAKHRRIANPAFHGEKLKGMVPAMVES 95

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1254009998 152 SKILIQKL-CCLGVADEEVDVLSVITLCTLDIICETSMG 189
Cdd:cd11052    96 VSDMLERWkKQMGEEGEEVDVFEEFKALTADIISRTAFG 134

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 104 FAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQSKILIQKLCCLGVADEEVDVLSVITLCTLDII 183
Cdd:cd11055    39 PLFILLDEPFDSSLLFLKGERWKRLRTTLSPTFSSGKLKLMVPIINDCCDELVEKLEKAAETGKPVDMKDLFQGFTLDVI 118

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1254009998 184 CETSMGKAIGAQLAENNEyvwAVHTINKLISKRTNNPLM-----WNSFIYNLTEDGRTHEKCLHILHDFTKKVIVERKE 257
Cdd:cd11055   119 LSTAFGIDVDSQNNPDDP---FLKAAKKIFRNSIIRLFLllllfPLRLFLFLLFPFVFGFKSFSFLEDVVKKIIEQRRK 194

cytochrome P450 family 734; Cytochrome P450 family 734 (CYP734) 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. CYP734As function as multisubstrate and multifunctional enzymes in brassinosteroid (BRs) catabolism and regulation of BRs homeostasis. Arabidopsis thaliana CYP734A1/BAS1 (formerly CYP72B1) inactivates bioactive brassinosteroids such as castasterone (CS) and brassinolide (BL) by C-26 hydroxylation. Rice CYP734As can catalyze C-22 hydroxylation as well as second and third oxidations to produce aldehyde and carboxylate groups at C-26. CYP734 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  70 RMCLLWIGPFPCLMLYSADLVEPIFS-STKHLNKGFAYVLLEPWLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPIF 148
Cdd:cd20639    13 KTFLYWFGPTPRLTVADPELIREILLtRADHFDRYEAHPLVRQLEGDGLVSLRGEKWAHHRRVITPAFHMENLKRLVPHV 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1254009998 149 NEQSKILIQKLCCLGVADE--EVDVLSVITLCTLDIICETSMGK 190
Cdd:cd20639    93 VKSVADMLDKWEAMAEAGGegEVDVAEWFQNLTEDVISRTAFGS 136

cytochrome P450 family 72; Cytochrome P450 family 72 (CYP72) 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. Characterized members, among others, include: Catharanthus roseus cytochrome P450 72A1 (CYP72A1), also called secologanin synthase (EC 1.3.3.9), that catalyzes the conversion of loganin into secologanin, the precursor of monoterpenoid indole alkaloids and ipecac alkaloids; Medicago truncatula CYP72A67 that catalyzes a key oxidative step in hemolytic sapogenin biosynthesis; and Arabidopsis thaliana CYP72C1, an atypical CYP that acts on brassinolide precursors and functions as a brassinosteroid-inactivating enzyme. This family also includes Panax ginseng CYP716A47 that catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis. CYP72 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998  70 RMCLLWIGPFPCLMLYSADLVEPIFS--STKHLNKGFAYVLLepwLGISILTSQKEQWRPKRKLLTPTFHYDILKDFLPI 147
Cdd:cd20642    13 KNSFTWFGPIPRVIIMDPELIKEVLNkvYDFQKPKTNPLTKL---LATGLASYEGDKWAKHRKIINPAFHLEKLKNMLPA 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1254009998 148 FNEQSKILIQKLCCLGVADE--EVDVLSVITLCTLDIICETSMG 189
Cdd:cd20642    90 FYLSCSEMISKWEKLVSSKGscELDVWPELQNLTSDVISRTAFG 133

unknown subfamily of cytochrome P450s; This subfamily is composed of uncharacterized cytochrome P450s. Cytochrome P450 (P450, CYP) is a large 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. Their monooxygenase activity relies on the reductive scission of molecular oxygen bound to the P450 heme iron, and the delivery of two electrons to the heme iron during the catalytic cycle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 107 VLLEpwLGIS-ILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQSKILIQKLCCLGVADEEVDVLSVITLCTLDIICE 185
Cdd:cd11083    42 VFRE--MGINgVFSAEGDAWRRQRRLVMPAFSPKHLRYFFPTLRQITERLRERWERAAAEGEAVDVHKDLMRYTVDVTTS 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 186 TSMGKAI------GAQLAENNEYVWAVhtinklISKRTNNPLMWNSFIyNLTEDgRTHEKCLHILHDFTKKVIVERKEAL 259
Cdd:cd11083   120 LAFGYDLntlergGDPLQEHLERVFPM------LNRRVNAPFPYWRYL-RLPAD-RALDRALVEVRALVLDIIAAARARL 191

                  ..
gi 1254009998 260 QD 261
Cdd:cd11083   192 AA 193

cytochrome P450 family 52; Cytochrome P450 52 (CYP52), also called P450ALK, monooxygenases catalyze the first hydroxylation step in the assimilation of alkanes and fatty acids by filamentous fungi. The number of CYP52 proteins depend on the fungal species: for example, Candida tropicalis has seven, Candida maltose has eight, and Yarrowia lipolytica has twelve. The CYP52 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 111 PWLGISILTSQKEQWRPKRKLLTPTFHYDILKDfLPIFNEQSKILIQKlccLGVADEEVDVLSVITLCTLDIICETSMGK 190
Cdd:cd11063    46 PLLGDGIFTSDGEEWKHSRALLRPQFSRDQISD-LELFERHVQNLIKL---LPRDGSTVDLQDLFFRLTLDSATEFLFGE 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 191 AIGAQLA-----ENNEYVWAVHTINKLISKRTN-NPLMWnsFIYNltedgRTHEKCLHILHDFTKKVIverKEALQDSDY 264
Cdd:cd11063   122 SVDSLKPggdspPAARFAEAFDYAQKYLAKRLRlGKLLW--LLRD-----KKFREACKVVHRFVDPYV---DKALARKEE 191

                  .
gi 1254009998 265 K 265
Cdd:cd11063   192 S 192

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1254009998 114 GISIltSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQSKILIQKLCCLGVADEEVDVLSVITLCTLDIICETSMGKAI 192
Cdd:cd20650    51 AISI--AEDEEWKRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVKNLRKEAEKGKPVTLKDVFGAYSMDVITSTSFGVNI 127

cytochrome P450 family 5, subfamily A, polypeptide 1, also called thromboxane-A synthase; Cytochrome P450 5A1 (CYP5A1), also called thromboxane-A synthase (EC 5.3.99.5) or thromboxane synthetase, converts prostaglandin H2 into thromboxane A2, a biologically active metabolite of arachidonic acid that has been implicated in stroke, asthma, and various cardiovascular diseases, due to its acute and chronic effects in promoting platelet aggregation, vasoconstriction, bronchoconstriction, and proliferation. CYP5A1 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1254009998 116 SILTSQKEQWRPKRKLLTPTFHYDILKDFLPIFNEQSKILIQKLCCLGVADEEVDVLSVITLCTLDIICETSMGKAIGAQ 195
Cdd:cd20649    51 SLLCLRDERWKRVRSILTPAFSAAKMKEMVPLINQACDVLLRNLKSYAESGNAFNIQRCYGCFTMDVVASVAFGTQVDSQ 130

                  ....*...
gi 1254009998 196 LAENNEYV 203
Cdd:cd20649   131 KNPDDPFV 138