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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd20678 246 TFMFEGHDTTASGISWILYCLALHPEHQQRCREEIREILGDGDSITWEHLDQMPYTTMCIKEALRLYPPVPGISRELSKP 325

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296449    81 VTFPDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSA--QHSHAFLPFSGGSRNC 141
Cdd:cd20678 326 VTFPDGRSLPAGITVSLSIYGLHHNPAVWPNPEVFDPLRFSPENSskRHSHAFLPFSAGPRNC 388

cytochrome P450 family 4, subfamily B and similar cytochrome P450s, including subfamilies A, T, X, and Z; This group is composed of family 4 cytochrome P450s from subfamilies A (CYP4A), B (CYP4B), T (CYP4T), X (CYP4X), and Z (CYP4Z). The CYP4A, CYP4X, and CYP4Z subfamilies are specific to mammals, CYP4T is present in fish, while CYP4B is conserved among vertebrates. CYP4As are known for catalyzing arachidonic acid to 20-HETE (20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid), and some can also metabolize lauric and palmitic acid. CYP4Bs specialize in omega-hydroxylation of short chain fatty acids and also participates in the metabolism of exogenous compounds that are protoxic including valproic acid (C8), 3-methylindole (C9), 4-ipomeanol, 3-methoxy-4-aminoazobenzene, and several aromatic amines. CYP4X1 is expressed at high levels in the mammalian brain and may play a role in regulating fat metabolism. CYP4Z1 is a fatty acid hydroxylase that is unique among human CYPs in that it is predominantly expressed in the mammary gland. Monophyly was not found with the CYP4T and CYP4B subfamilies, and further consideration should be given to their nomenclature. The CYP4B-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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd20678 246 TFMFEGHDTTASGISWILYCLALHPEHQQRCREEIREILGDGDSITWEHLDQMPYTTMCIKEALRLYPPVPGISRELSKP 325

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296449    81 VTFPDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSA--QHSHAFLPFSGGSRNC 141
Cdd:cd20678 326 VTFPDGRSLPAGITVSLSIYGLHHNPAVWPNPEVFDPLRFSPENSskRHSHAFLPFSAGPRNC 388

Cytochrome P450 [Secondary metabolites biosynthesis, transport and catabolism, Defense mechanisms]; Cytochrome P450 is part of the Pathway/BioSystem: Biotin biosynthesis

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIhgllgdgasitwnhldqmPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:COG2124 233 LLLLAGHETTANALAWALYALLRHPEQLARLRAEP------------------ELLPAAVEETLRLYPPVPLLPRTATED 294

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296449    81 VTFpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRfapgsaqHSHAFLPFSGGSRNC 141
Cdd:COG2124 295 VEL-GGVTIPAGDRVLLSLAAANRDPRVFPDPDRFDPDR-------PPNAHLPFGGGPHRC 347

cytochrome P450 family 4, subfamily B and similar cytochrome P450s, including subfamilies A, T, X, and Z; This group is composed of family 4 cytochrome P450s from subfamilies A (CYP4A), B (CYP4B), T (CYP4T), X (CYP4X), and Z (CYP4Z). The CYP4A, CYP4X, and CYP4Z subfamilies are specific to mammals, CYP4T is present in fish, while CYP4B is conserved among vertebrates. CYP4As are known for catalyzing arachidonic acid to 20-HETE (20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid), and some can also metabolize lauric and palmitic acid. CYP4Bs specialize in omega-hydroxylation of short chain fatty acids and also participates in the metabolism of exogenous compounds that are protoxic including valproic acid (C8), 3-methylindole (C9), 4-ipomeanol, 3-methoxy-4-aminoazobenzene, and several aromatic amines. CYP4X1 is expressed at high levels in the mammalian brain and may play a role in regulating fat metabolism. CYP4Z1 is a fatty acid hydroxylase that is unique among human CYPs in that it is predominantly expressed in the mammary gland. Monophyly was not found with the CYP4T and CYP4B subfamilies, and further consideration should be given to their nomenclature. The CYP4B-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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd20678 246 TFMFEGHDTTASGISWILYCLALHPEHQQRCREEIREILGDGDSITWEHLDQMPYTTMCIKEALRLYPPVPGISRELSKP 325

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296449    81 VTFPDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSA--QHSHAFLPFSGGSRNC 141
Cdd:cd20678 326 VTFPDGRSLPAGITVSLSIYGLHHNPAVWPNPEVFDPLRFSPENSskRHSHAFLPFSAGPRNC 388

cytochrome P450 family 4; Cytochrome P450 family 4 (CYP4) proteins catalyze the omega-hydroxylation of the terminal carbon of fatty acids, including essential signaling molecules such as eicosanoids, prostaglandins and leukotrienes, and they are important for chemical defense. There are seven vertebrate family 4 subfamilies: CYP4A, CYP4B, CYP4F, CYP4T, CYP4V, CYP4X, and CYP4Z; three (CYP4X, CYP4A, CYP4Z) are specific to mammals. CYP4 enzymes metabolize fatty acids off various length, level of saturation, and branching. Specific subfamilies show preferences for the length of fatty acids; CYP4B, CYP4A and CYP4V, and CYP4F preferentially metabolize short (C7-C10), medium (C10-C16), and long to very long (C18-C26) fatty acid chains, respectively. CYP4 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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLG-DGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELST 79
Cdd:cd20628 236 TFMFAGHDTTASAISFTLYLLGLHPEVQEKVYEELDEIFGdDDRRPTLEDLNKMKYLERVIKETLRLYPSVPFIGRRLTE 315

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296449    80 PVTFpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQ--HSHAFLPFSGGSRNC 141
Cdd:cd20628 316 DIKL-DGYTIPKGTTVVISIYALHRNPEYFPDPEKFDPDRFLPENSAkrHPYAYIPFSAGPRNC 378

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296449       1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVP-GISRELST 79
Cdd:pfam00067 268 ELFFAGTDTTSSTLSWALYELAKHPEVQEKLREEIDEVIGDKRSPTYDDLQNMPYLDAVIKETLRLHPVVPlLLPREVTK 347

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296449      80 PVTFPdGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAP--GSAQHSHAFLPFSGGSRNC 141
Cdd:pfam00067 348 DTVIP-GYLIPKGTLVIVNLYALHRDPEVFPNPEEFDPERFLDenGKFRKSFAFLPFGAGPRNC 410

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGAsITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd20620 219 TLFLAGHETTANALSWTWYLLAQHPEVAARLRAEVDRVLGGRP-PTAEDLPQLPYTEMVLQESLRLYPPAWIIGREAVED 297

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296449    81 VTFPDGRsLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQ--HSHAFLPFSGGSRNC 141
Cdd:cd20620 298 DEIGGYR-IPAGSTVLISPYVTHRDPRFWPDPEAFDPERFTPEREAarPRYAYFPFGGGPRIC 359

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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd11055 233 IFLLAGYETTSNTLSFASYLLATNPDVQEKLIEEIDEVLPDDGSPTYDTVSKLKYLDMVINETLRLYPPAFFISRECKED 312

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296449    81 VTFpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQ--HSHAFLPFSGGSRNC 141
Cdd:cd11055 313 CTI-NGVFIPKGVDVVIPVYAIHHDPEFWPDPEKFDPERFSPENKAkrHPYAYLPFGAGPRNC 374

cytochrome P450 family 6 and similar cytochrome P450s; This family is composed of cytochrome P450s from insects and crustaceans, including the CYP6, CYP9 and CYP310 subfamilies, which are involved in the metabolism of insect hormones and xenobiotic detoxification. The CYP6-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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGD-GASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELST 79
Cdd:cd11056 236 VFFLAGFETSSSTLSFALYELAKNPEIQEKLREEIDEVLEKhGGELTYEALQEMKYLDQVVNETLRKYPPLPFLDRVCTK 315

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296449    80 PVTFPDGR-SLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPG--SAQHSHAFLPFSGGSRNC 141
Cdd:cd11056 316 DYTLPGTDvVIEKGTPVIIPVYALHHDPKYYPEPEKFDPERFSPEnkKKRHPYTYLPFGDGPRNC 380

cytochrome P450 family 24 subfamily A, polypeptide 1 and similar cytochrome P450s; This family is composed of vertebrate cytochrome P450 24A1 (CYP24A1) and similar proteins including several Drosophila proteins such as CYP315A1 (also called protein shadow) and CYP314A1 (also called ecdysone 20-monooxygenase), and vertebrate CYP11 and CYP27 subfamilies. Both CYP314A1 and CYP315A1, which has ecdysteroid C2-hydroxylase activity, are involved in the metabolism of insect hormones. CYP24A1 and CYP27B1 have roles in calcium homeostasis and metabolism, and the regulation of vitamin D. CYP24A1 catabolizes calcitriol (1,25(OH)2D), the physiologically active vitamin D hormone, by catalyzing its hydroxylation, while CYP27B1 is a calcidiol 1-monooxygenase that coverts 25-hydroxyvitamin D3 to calcitriol. The CYP24A1-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 296449     2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTPV 81
Cdd:cd11054 239 LLLAGVDTTSNTLAFLLYHLAKNPEVQEKLYEEIRSVLPDGEPITAEDLKKMPYLKACIKESLRLYPVAPGNGRILPKDI 318

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296449    82 TFpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRF----APGSAQHSHAFLPFSGGSRNC 141
Cdd:cd11054 319 VL-SGYHIPKGTLVVLSNYVMGRDEEYFPDPEEFIPERWlrddSENKNIHPFASLPFGFGPRMC 381

cytochrome P450 families 1 and 2, and similar cytochrome P450s; This model includes cytochrome P450 families 1 (CYP1) and 2 (CYP2), CYP17A1, and CYP21 in vertebrates, as well as insect and crustacean CYPs similar to CYP15A1 and CYP306A1. CYP1 and CYP2 enzymes are involved in the metabolism of endogenous and exogenous compounds such as hormones, xenobiotics, and drugs. CYP17A1 catalyzes the conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products, while CYP21 catalyzes the 21-hydroxylation of steroids such as progesterone and 17-alpha-hydroxyprogesterone (17-alpha-OH-progesterone) to form 11-deoxycorticosterone and 11-deoxycortisol, respectively. Members of this 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 296449     2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVP-GISRELSTP 80
Cdd:cd20617 231 LFLAGTDTTSTTLEWFLLYLANNPEIQEKIYEEIDNVVGNDRRVTLSDRSKLPYLNAVIKEVLRLRPILPlGLPRVTTED 310

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 296449    81 VTFpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRF-APGSAQHSHAFLPFSGGSRNC 141
Cdd:cd20617 311 TEI-GGYFIPKGTQIIINIYSLHRDEKYFEDPEEFNPERFlENDGNKLSEQFIPFGIGKRNC 371

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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd11046 247 TMLIAGHETTAAVLTWTLYELSQNPELMAKVQAEVDAVLGDRLPPTYEDLKKLKYTRRVLNESLRLYPQPPVLIRRAVED 326

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 296449    81 VTFPDGR-SLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQHSH------AFLPFSGGSRNC 141
Cdd:cd11046 327 DKLPGGGvKVPAGTDIFISVYNLHRSPELWEDPEEFDPERFLDPFINPPNeviddfAFLPFGGGPRKC 394

cytochrome P450 family 51 and similar cytochrome P450s; This family is composed of cytochrome P450 51 (CYP51 or sterol 14alpha-demethylase) and related cytochrome P450s. CYP51 is the only cytochrome P450 enzyme with a conserved function across animals, fungi, and plants, in the synthesis of essential sterols. In mammals, it is expressed in many different tissues, with highest expression in testis, ovary, adrenal gland, prostate, liver, kidney, and lung. In fungi, CYP51 is a significant drug target for treatment of human protozoan infections. In plants, it functions within a specialized defense-related metabolic pathway. CYP51 is also found in several bacterial species. This 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 296449     2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGD-GASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd11042 220 LLFAGQHTSSATSAWTGLELLRNPEHLEALREEQKEVLGDgDDPLTYDVLKEMPLLHACIKETLRLHPPIHSLMRKARKP 299

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296449    81 VTFPDGR-SLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQHSH----AFLPFSGGSRNC 141
Cdd:cd11042 300 FEVEGGGyVIPKGHIVLASPAVSHRDPEIFKNPDEFDPERFLKGRAEDSKggkfAYLPFGAGRHRC 365

cytochrome P450 family 102, subfamily A, polypeptide 1, also called bifunctional cytochrome P450/NADPH--P450 reductase; Cytochrome P450 102A1, also called cytochrome P450(BM-3) or P450BM-3, is a bifunctional cytochrome P450/NADPH--P450 reductase. These proteins fuse an N-terminal cytochrome p450 with a C-terminal cytochrome p450 reductase (CYPOR). It functions as a fatty acid monooxygenase, catalyzing the hydroxylation of fatty acids at omega-1, omega-2 and omega-3 positions, with activity towards fatty acids with a chain length of 9-18 carbons. Its NADPH-dependent reductase activity (via the C-terminal domain) allows electron transfer from NADPH to the heme iron of the N-terminal cytochrome P450. CYP120A1 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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGAsITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd11068 237 TFLIAGHETTSGLLSFALYYLLKNPEVLAKARAEVDEVLGDDP-PPYEQVAKLRYIRRVLDETLRLWPTAPAFARKPKED 315

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296449    81 VTFPDGRSLPKGITVMLSIYGLHHNPKVW-PNPEVFDPSRFAPGSAQ--HSHAFLPFSGGSRNC 141
Cdd:cd11068 316 TVLGGKYPLKKGDPVLVLLPALHRDPSVWgEDAEEFRPERFLPEEFRklPPNAWKPFGNGQRAC 379

putative cytochrome P450 family 136 and similar cytochrome P450s; This group is composed of Mycobacterium tuberculosis putative cytochrome P450 136 (CYP136) and similar proteins. It 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 296449     3 MFEGHDTTASGISWILYALATHPKHQERCREEIHGLlGDGAsITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTPVT 82
Cdd:cd11045 220 MMAAHDTTTSTLTSMAYFLARHPEWQERLREESLAL-GKGT-LDYEDLGQLEVTDWVFKEALRLVPPVPTLPRRAVKDTE 297

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 296449    83 FpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSA---QHSHAFLPFSGGSRNC 141
Cdd:cd11045 298 V-LGYRIPAGTLVAVSPGVTHYMPEYWPNPERFDPERFSPERAedkVHRYAWAPFGGGAHKC 358

unknown subfamily of fungal cytochrome P450s; This subfamily is composed of uncharacterized fungal 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 296449     2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGD-GASITWNHLDQMPYTTMCIKEALRLYPPVPGI-SRELST 79
Cdd:cd11059 229 HIVAGHDTTAVTLTYLIWELSRPPNLQEKLREELAGLPGPfRGPPDLEDLDKLPYLNAVIRETLRLYPPIPGSlPRVVPE 308

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296449    80 PVTFPDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQHSH----AFLPFSGGSRNC 141
Cdd:cd11059 309 GGATIGGYYIPGGTIVSTQAYSLHRDPEVFPDPEEFDPERWLDPSGETARemkrAFWPFGSGSRMC 374

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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGaSITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd11052 239 TFFFAGHETTALLLTWTTMLLAIHPEWQEKAREEVLEVCGKD-KPPSDSLSKLKTVSMVINESLRLYPPAVFLTRKAKED 317

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296449    81 VTFpDGRSLPKGITVMLSIYGLHHNPKVWPN-PEVFDPSRFAPGSAQ---HSHAFLPFSGGSRNC 141
Cdd:cd11052 318 IKL-GGLVIPKGTSIWIPVLALHHDEEIWGEdANEFNPERFADGVAKaakHPMAFLPFGLGPRNC 381

cytochrome P450 family 56-like fungal cytochrome P450s; This group includes Saccharomyces cerevisiae cytochrome P450 56, also called cytochrome P450-DIT2, and similar fungal proteins. CYP56 is involved in spore wall maturation and is thought to catalyze the oxidation of tyrosine residues in the formation of LL-dityrosine-containing precursors of the spore wall. The CYP56-like 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 296449     2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNH--LDQMPYTTMCIKEALRLYPPVPGISRELST 79
Cdd:cd11070 231 FFIAGHETTANTLSFALYLLAKHPEVQDWLREEIDSVLGDEPDDWDYEedFPKLPYLLAVIYETLRLYPPVQLLNRKTTE 310

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296449    80 PVTFPDGRS----LPKGITVMLSIYGLHHNPKVW-PNPEVFDPSRFAPGS-----AQHSH----AFLPFSGGSRNC 141
Cdd:cd11070 311 PVVVITGLGqeivIPKGTYVGYNAYATHRDPTIWgPDADEFDPERWGSTSgeigaATRFTpargAFIPFSAGPRAC 386

cytochrome P450 family 17, subfamily A, polypeptide 1, and similar cytochrome P450s; This subfamily contains cytochrome P450 17A1 (CYP17A1 or Cyp17a1), cytochrome P450 21 (CYP21 or Cyp21) and similar proteins. CYP17A1, also called cytochrome P450c17, steroid 17-alpha-hydroxylase (EC 1.14.14.19)/17,20 lyase (EC 1.14.14.32), or 17-alpha-hydroxyprogesterone aldolase, catalyzes the conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione; it catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. This subfamily also contains CYP21, also called steroid 21-hydroxylase (EC 1.14.14.16) or cytochrome P-450c21 or CYP21A2, catalyzes the 21-hydroxylation of steroids and is required for the adrenal synthesis of mineralocorticoids and glucocorticoids. The CYP17A1-like 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 296449     2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVP-GISRELSTP 80
Cdd:cd11027 237 IFGAGTETTATTLRWAIAYLVNYPEVQAKLHAELDDVIGRDRLPTLSDRKRLPYLEATIAEVLRLSSVVPlALPHKTTCD 316

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296449    81 VTFpDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAQ---HSHAFLPFSGGSRNC 141
Cdd:cd11027 317 TTL-RGYTIPKGTTVLVNLWALHHDPKEWDDPDEFRPERFLDENGKlvpKPESFLPFSAGRRVC 379

cytochrome P450 family 59 and similar cytochrome P450s; This family is composed of Aspergillus nidulans cytochrome P450 59 (CYP59), also called sterigmatocystin biosynthesis P450 monooxygenase stcS, and similar fungal proteins. CYP59 is required for the conversion of versicolorin A to sterigmatocystin. This 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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITW-------NHLDQMPYTTMCIKEALRLYPPVpGI 73
Cdd:cd11051 192 TFLFAGHDTTSSTLCWAFYLLSKHPEVLAKVRAEHDEVFGPDPSAAAellregpELLNQLPYTTAVIKETLRLFPPA-GT 270

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296449    74 SRELS--TPVTFPDGRSLP-KGITVMLSIYGLHHNPKVWPNPEVFDPSRF--APGSAQH--SHAFLPFSGGSRNC 141
Cdd:cd11051 271 ARRGPpgVGLTDRDGKEYPtDGCIVYVCHHAIHRDPEYWPRPDEFIPERWlvDEGHELYppKSAWRPFERGPRNC 345

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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGISRELSTP 80
Cdd:cd20639 239 TFFFAGKETTSNLLTWTTVLLAMHPEWQERARREVLAVCGKGDVPTKDHLPKLKTLGMILNETLRLYPPAVATIRRAKKD 318

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296449    81 VTFpDGRSLPKGITVMLSIYGLHHNPKVW-PNPEVFDPSRFAPGS---AQHSHAFLPFSGGSRNC 141
Cdd:cd20639 319 VKL-GGLDIPAGTELLIPIMAIHHDAELWgNDAAEFNPARFADGVaraAKHPLAFIPFGLGPRTC 382

cytochrome P450; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296449      2 FMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVP-GISRELSTP 80
Cdd:PTZ00404 291 FFLAGVDTSATSLEWMVLMLCNYPEIQEKAYNEIKSTVNGRNKVLLSDRQSTPYTVAIIKETLRYKPVSPfGLPRSTSND 370

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296449     81 VTFPDGRSLPKGITVMLSIYGLHHNPKVWPNPEVFDPSRFAPGSAqhSHAFLPFSGGSRNC 141
Cdd:PTZ00404 371 IIIGGGHFIPKDAQILINYYSLGRNEKYFENPEQFDPSRFLNPDS--NDAFMPFSIGPRNC 429

cytochrome P450 monooxygenase CYP5011A1 and similar cytochrome P450s; This subfamily is composed of CYPs from unicellular ciliates similar to Tetrahymena thermophila CYP5011A1, whose function is still unknown. It 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 296449     1 TFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPG-ISRELST 79
Cdd:cd20621 236 TFFFAGTDTTGHLVGMCLYYLAKYPEIQEKLRQEIKSVVGNDDDITFEDLQKLNYLNAFIKEVLRLYNPAPFlFPRVATQ 315