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 112214297   1 YWVVTRYEDVKAVFRDNLVFSPAIALEKITPVSEEatatlarYDYAMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEA 80
Cdd:cd11078   21 YWVVSRYEDVKAVLRDPQTFSSAGGLTPESPLWPE-------AGFAPTPSLVNEDPPRHTRLRRLVSRAFTPRRIAALEP 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  81 MVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHTVNTWGRPAPEEQVAVAEAVGRFWQ 160
Cdd:cd11078   94 RIRELAAELLDRLAEDGRADFVADFAAPLPALVIAELLGVPEEDMERFRRWADAFALVTWGRPSEEEQVEAAAAVGELWA 173

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 112214297 161 YAGTVLEKMRQDPSGHGWMPYgIRMQQQMPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd11078  174 YFADLVAERRREPRDDLISDL-LAAADGDGERLTDEELVAFLFLLLVAGHETT 225

cytochrome P450 family 130-like and similar cytochrome P450s; This subfamily includes Mycobacterium tuberculosis cytochrome P450 130 (CYP130), Rhodococcus erythropolis CYP116, and similar bacterial proteins. CYP130 catalyzes the N-demethylation of dextromethorphan, and has also shown a natural propensity to bind primary arylamines. CYP116 is involved in the degradation of thiocarbamate herbicides. The CYP130-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 112214297   1 YWVVTRYEDVKAVFRDNLVFSPAIALEKITPVSEEatatlarYDYAMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEA 80
Cdd:cd11078   21 YWVVSRYEDVKAVLRDPQTFSSAGGLTPESPLWPE-------AGFAPTPSLVNEDPPRHTRLRRLVSRAFTPRRIAALEP 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  81 MVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHTVNTWGRPAPEEQVAVAEAVGRFWQ 160
Cdd:cd11078   94 RIRELAAELLDRLAEDGRADFVADFAAPLPALVIAELLGVPEEDMERFRRWADAFALVTWGRPSEEEQVEAAAAVGELWA 173

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 112214297 161 YAGTVLEKMRQDPSGHGWMPYgIRMQQQMPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd11078  174 YFADLVAERRREPRDDLISDL-LAAADGDGERLTDEELVAFLFLLLVAGHETT 225

cytochrome P450 family 130-like and similar cytochrome P450s; This subfamily includes Mycobacterium tuberculosis cytochrome P450 130 (CYP130), Rhodococcus erythropolis CYP116, and similar bacterial proteins. CYP130 catalyzes the N-demethylation of dextromethorphan, and has also shown a natural propensity to bind primary arylamines. CYP116 is involved in the degradation of thiocarbamate herbicides. The CYP130-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 112214297   1 YWVVTRYEDVKAVFRDNLVFSPAIALEKITPVSEEatatlarYDYAMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEA 80
Cdd:cd11078   21 YWVVSRYEDVKAVLRDPQTFSSAGGLTPESPLWPE-------AGFAPTPSLVNEDPPRHTRLRRLVSRAFTPRRIAALEP 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  81 MVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHTVNTWGRPAPEEQVAVAEAVGRFWQ 160
Cdd:cd11078   94 RIRELAAELLDRLAEDGRADFVADFAAPLPALVIAELLGVPEEDMERFRRWADAFALVTWGRPSEEEQVEAAAAVGELWA 173

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 112214297 161 YAGTVLEKMRQDPSGHGWMPYgIRMQQQMPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd11078  174 YFADLVAERRREPRDDLISDL-LAAADGDGERLTDEELVAFLFLLLVAGHETT 225

cytochrome P450 family 142 and similar cytochrome P450s; This family is composed of cytochrome P450s (CYPs) with similarity to Streptomyces sp. P450sky (also called CYP163B3), Sphingopyxis macrogoltabida P450pyr hydroxylase, Novosphingobium aromaticivorans CYP108D1, Pseudomonas sp. cytochrome P450-Terp (P450terp), and Amycolatopsis balhimycina P450 OxyD, as well as several Mycobacterium proteins CYP124, CYP125, CYP126, and CYP142. P450sky is involved in the hydroxylation of three beta-hydroxylated amino acid precursors required for the biosynthesis of the cyclic depsipeptide skyllamycin. P450pyr hydroxylase is an active and selective catalyst for the regio- and stereo-selective hydroxylation at non-activated carbon atoms with a broad substrate range. P450terp catalyzes the hydroxylation of alpha-terpineol as part of its catabolic assimilation. OxyD is involved in beta-hydroxytyrosine formation during vancomycin biosynthesis. CYP124 is a methyl-branched lipid omega-hydroxylase while CYP142 is a cholesterol 27-oxidase with likely roles in host response modulation and cholesterol metabolism. 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 112214297   1 YWVVTRYEDVKAVFRDNLVFS--PAIALEKITPVSEeatatlaryDYAMARTLVNEDEPAHMPRRRALMDPFTPKELAHH 78
Cdd:cd11033   22 FWAVTRHADVVAVSRDPELFSsaRGGVLIDLPEEDA---------DPAAGRMLINMDPPRHTRLRRLVSRAFTPRAVARL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  79 EAMVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHTVNTWGRPAPEEQVAVAEAVGRF 158
Cdd:cd11033   93 EDRIRERARRLVDRALARGECDFVEDVAAELPLQVIADLLGVPEEDRPKLLEWTNELVGADDPDYAGEAEEELAAALAEL 172

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 112214297 159 WQYAGTVLEKMRQDPSGH--GWMPYGIRMQQQMPDVVTDSYLHSMmmagIVAAHETT 213
Cdd:cd11033  173 FAYFRELAEERRANPGDDliSVLANAEVDGEPLTDEEFASFFILL----AVAGNETT 225

P450cam and similar cytochrome P450s; This family is composed of cytochrome P450s (CYPs) with similarity to Pseudomonas putida P450cam and Cyp101 proteins from Novosphingobium aromaticivorans such as CYP101C1 and CYP101D2. P450cam catalyzes the hydroxylation of camphor in a process that involves two electron transfers from the iron-sulfur protein, putidaredoxin. CYP101D2 is capable of oxidizing camphor while CYP101C1 does not bind camphor but is capable of binding and hydroxylating ionone derivatives such as alpha- and beta-ionone and beta-damascone. 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 112214297   1 YWVVTRYEDVKAVFRDNLVFSPaialEKITPVSEEATAtlarydYAMARTLVneDEPAHMPRRRALMDPFTPKELAHHEA 80
Cdd:cd11035   15 HWIVTRGEDIREVLRDPETFSS----RVITVPPPAGEP------YPLIPLEL--DPPEHTRYRRLLNPLFSPKAVAALEP 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  81 MVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHTvntwgrpAPEEQVAVAEAVGRFWQ 160
Cdd:cd11035   83 RIRERAVELIESFAPRGECDFVADFAEPFPTRVFLELMGLPLEDLDRFLEWEDAML-------RPDDAEERAAAAQAVLD 155

                        170
                 ....*....|...
gi 112214297 161 YAGTVLEKMRQDP 173
Cdd:cd11035  156 YLTPLIAERRANP 168

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 112214297   2 WVVTRYEDVKAVFRDNLVFSPAIALEKITPVSeeatatlarydyAMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEAM 81
Cdd:cd00302   14 VVVSDPELVREVLRDPRDFSSDAGPGLPALGD------------FLGDGLLTLDGPEHRRLRRLLAPAFTPRALAALRPV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  82 VRRLTREYVDRFVESG-KADLVDEMLWEVPLTVALHFLGVPE--EDMATMRKYSIAHT----VNTWGRPAPEEQVAVAEA 154
Cdd:cd00302   82 IREIARELLDRLAAGGeVGDDVADLAQPLALDVIARLLGGPDlgEDLEELAELLEALLkllgPRLLRPLPSPRLRRLRRA 161

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 112214297 155 VGRFWQYAGTVLEKMRQDPsgHGWMPYGIRMQQQMPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd00302  162 RARLRDYLEELIARRRAEP--ADDLDLLLLADADDGGGLSDEEIVAELLTLLLAGHETT 218

cytochrome P450 family 158, subfamily A and similar cytochrome P450s; This family is composed of cytochrome P450s (CYPs) with similarity to Streptomyces coelicolor CYP158A1 and CYP158A2, Streptomyces natalensis PimD (also known as CYP107E), Mycobacterium tuberculosis CYP121, and Micromonospora griseorubida MycG (also known as CYP107B). CYP158A1 and CYP158A2 catalyze an unusual oxidative C-C coupling reaction to polymerize flaviolin and form highly conjugated pigments; CYP158A2 produces three isomers of biflaviolin and one triflaviolin while CYP158A1 produces only two isomers of biflaviolin. PimD is a cytochrome P450 monooxygenase with native epoxidase activity that is critical in the biosynthesis of the polyene macrolide antibiotic pimaricin. CYP121 is essential for the viability of M. tuberculosis and is a novel drug target for the inhibition of mycobacterial growth. MycG catalyzes both hydroxylation and epoxidation reactions in the biosynthesis of the 16-membered ring macrolide antibiotic mycinamicin II. 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 112214297   2 WVVTRYEDVKAVFRDNLvFSPAIALEKITPVSEEATatlarydyAMARTLVNEDEPAHMPRRRALMDPFTPKelaHHEAM 81
Cdd:cd11031   26 WLVTRYADVRQVLADPR-FSRAAAAPPDAPRLTPEP--------LLPGSLMSMDPPEHTRLRRLVAKAFTAR---RVERL 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  82 ---VRRLTREYVDRFVESGK-ADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAhtVNTWGRPAPEEqvaVAEAVGR 157
Cdd:cd11031   94 rprIEEIADELLDAMEAQGPpADLVEALALPLPVAVICELLGVPYEDRERFRAWSDA--LLSTSALTPEE---AEAARQE 168

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 112214297 158 FWQYAGTVLEKMRQDP---------SGHGwmpygirmqqqMPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd11031  169 LRGYMAELVAARRAEPgddllsalvAARD-----------DDDRLSEEELVTLAVGLLVAGHETT 222

cytochrome P450 family 107 and similar cytochrome P450s; This group contains bacterial cytochrome P450s from families 107 (CYP107), 154 (CYP154), 197 (CYP197), and similar proteins. Among the members of this group are: Pseudonocardia autotrophica vitamin D(3) 25-hydroxylase (also known as CYP197A; EC 1.14.15.15) that catalyzes the hydroxylation of vitamin D(3) into 25-hydroxyvitamin D(3) and 1-alpha,25-dihydroxyvitamin D(3), its physiologically active forms; Saccharopolyspora erythraea CYP107A1, also called P450eryF or 6-deoxyerythronolide B hydroxylase (EC 1.14.15.35), that catalyzes the conversion of 6-deoxyerythronolide B (6-DEB) to erythronolide B (EB) by the insertion of an oxygen at the 6S position of 6-DEB; Bacillus megaterium CYP107DY1 that displays C6-hydroxylation activity towards mevastatin to produce pravastatin; Streptomyces coelicolor CYP154C1 that shows activity towards 12- and 14-membered ring macrolactones in vitro and may be involved in catalyzing the site-specific oxidation of the precursors to macrolide antibiotics, which introduces regiochemical diversity into the macrolide ring system; and Nocardia farcinica CYP154C5 that acts on steroids with regioselectivity and stereoselectivity, converting various pregnans and androstans to yield 16 alpha-hydroxylated steroid products. Bacillus subtilis CYP107H1 is not included in this group. The CYP107-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 112214297   2 WVVTRYEDVKAVFRDN-LVFSPAIALEkitPVSEEATATLARYDYAMARTLVNEDEPAHMpRRRALMDP-FTPKELAHHE 79
Cdd:cd11029   26 WLVTRYDDARAALADPrLSKDPRKAWP---AFRGRAPGAPPDLPPVLSDNMLTSDPPDHT-RLRRLVAKaFTPRRVEALR 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  80 AMVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSiahTVNTWGRPAPEEqvaVAEAVGRFW 159
Cdd:cd11029  102 PRIEEITDELLDALAARGVVDLVADFAYPLPITVICELLGVPEEDRDRFRRWS---DALVDTDPPPEE---AAAALRELV 175

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 112214297 160 QYAGTVLEKMRQDPSGH--GWMpygIRMQQQmPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd11029  176 DYLAELVARKRAEPGDDllSAL---VAARDE-GDRLSEEELVSTVFLLLVAGHETT 227

cytochrome P450 family 199, subfamily A, polypeptide 2 and similar cytochrome P450s; This family is composed of cytochrome P450s (CYPs) with similarity to Rhodopseudomonas palustris CYP199A2 and CYP199A4. CYP199A2 catalyzes the oxidation of aromatic carboxylic acids including indole-2-carboxylic acid, 2-naphthoic acid and 4-ethylbenzoic acid. CYP199A4 catalyzes the hydroxylation of para-substituted benzoic acids. 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 112214297   1 YWVVTRYEDVKAVFRDNLVFSpaialekitpvSEEATATLARYDYAMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEA 80
Cdd:cd11037   23 VYALARYDEVRAALRDHETFS-----------SARGVGLNDFLNWRLPGSILASDPPEHDRLRAVLSRPLSPRALRKLRD 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  81 MVRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSiAHTVNTWGrPAPEEQVAVAEAVGRFWQ 160
Cdd:cd11037   92 RIEEAADELVDELVARGEFDAVTDLAEAFPLRVVPDLVGLPEEGRENLLPWA-AATFNAFG-PLNERTRAALPRLKELRD 169

                        170
                 ....*....|....*..
gi 112214297 161 YAGTVLEKMRQDPSGHG 177
Cdd:cd11037  170 WVAEQCARERLRPGGWG 186

cytochrome P450 AurH and similar cytochrome P450s; This group includes Streptomyces thioluteus P450 monooxygenase AurH which is uniquely capable of forming a homochiral tetrahydrofuran ring, a vital component of the polyketide antibiotic aureothin. AurH catalyzes an unprecedented tandem oxygenation process: first, it catalyzes an asymmetric hydroxylation of deoxyaureothin to yield (7R)-7-hydroxydeoxyaureothin as an intermediate; and second, it mediates another C-O bond formation that leads to O-heterocyclization. The AurH-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 112214297   2 WVVTRYEDVKAVFRDNLVFSPAIALEKITPVSEeatATLARYdyaMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEAM 81
Cdd:cd11038   28 LAVLRYEEVGQLLRDRRLRQGGHRWLAMNGVTE---GPFADW---WVDFLLSLEGADHARLRGLVNPAFTPKAVEALRPR 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  82 VRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATmrkysIAHTVNTWGR----PAPEEQVAVAEAVGR 157
Cdd:cd11038  102 FRATANDLIDGFAEGGECEFVEAFAEPYPARVICTLLGLPEEDWPR-----VHRWSADLGLafglEVKDHLPRIEAAVEE 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 112214297 158 FWQYAGTVLEKMRQDPsGHGWMPYGIRMQQQmPDVVTDSYLHSMMMAGIVAAHETT 213
Cdd:cd11038  177 LYDYADALIEARRAEP-GDDLISTLVAAEQD-GDRLSDEELRNLIVALLFAGVDTT 230

unknown subfamily of mostly bacterial cytochrome P450s; This subfamily is composed of uncharacterized cytochrome P450s, predominantly from bacteria. 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 112214297   2 WVVTRYEDVKAVFRDNLVFSPAIAlekitpvseeatatlarydyAMARTLVNEDEPAHMPRRRALMDPFTPKELAHHEAM 81
Cdd:cd11079   11 WVVLRHADVKAAAEDPETFSSAVS--------------------ARLSVPNGMDPPEHTAYRAAIDRYFTPERLARFEPV 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297  82 VRRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHTVNTWGRPApEEQVAVAEavgRFWQY 161
Cdd:cd11079   71 CRRVAARLVAELPAGGGGDVVGQFAQPFAVRVQTAFLGWPAALERPLAEWVNKNHAATRSGDR-AATAEVAE---EFDGI 146

                        170
                 ....*....|...
gi 112214297 162 AGTVLEKMRQDPS 174
Cdd:cd11079  147 IRDLLADRRAAPR 159

cytochrome P450 BJ-4 homolog and similar cytochrome P450s; This group is composed of mostly uncharacterized proteins including Sinorhizobium fredii CYPBJ-4 homolog. 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 112214297  46 AMARTLVNEDEPAHMPRRRALMDPFTPKELAHHE--AMVRRLTREYVDRFVESGKADLVDEMLwEVPLTVALHFLGVPEE 123
Cdd:cd20614   53 ILGGTMAAQDGALHRRARAASNPSFTPKGLSAAGvgALIAEVIEARIRAWLSRGDVAVLPETR-DLTLEVIFRILGVPTD 131

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112214297 124 DMATMRKY-------SIAHTVNTWGRPAPEEQVAvaeavgRFW--QYAGTVLEKMRQDPSGHGWMPYGIRMQQQMPDVVT 194
Cdd:cd20614  132 DLPEWRRQyrelflgVLPPPVDLPGMPARRSRRA------RAWidARLSQLVATARANGARTGLVAALIRARDDNGAGLS 205

                        170
                 ....*....|....*....
gi 112214297 195 DSYLHSMMMAGIVAAHETT 213
Cdd:cd20614  206 EQELVDNLRLLVLAGHETT 224

cytochrome P450 XplA; XplA is a cytochrome P450 that was found to mediate the microbial metabolism of the military explosive, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). XplA has an unusual structural organization comprising a heme domain that is fused to its flavodoxin redox partner. XplA, along with its partner reductase XplB, are plasmid encoded and the xplA gene has now been found in divergent genera across the globe with near sequence identity. It has only been detected at explosive-contaminated sites, suggesting rapid dissemination of this novel catabolic activity, possibly within a 50-year period since the introduction of RDX into the environment. XplA 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 112214297   3 VVTRYEDVKAVFRDNLvfspaialeKITPVSEEATATLARYDyamaRTLVNEDEPAHMPRRRALMDPFTPKELAHHEAMV 82
Cdd:cd20619   12 LVSRYADVSHFAKLPI---------MSVEPGWADAGPWAVAS----DTALGSDPPHHTVLRRQTNKWFTPKLVDGWVRTT 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 112214297  83 RRLTREYVDRFVESGKADLVDEMLWEVPLTVALHFLGVPEEDMATMRKYSIAHT 136
Cdd:cd20619   79 RELVGDLLDGVEAGQVIEARRDLAVVPTHVTMARVLQLPEDDADAVMEAMFEAM 132