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drug target
the cytotoxicity of heteroaromatic N-oxides in murine hepatoma MH22a and human colon carcinoma HCT-116 cells increases with the geometric average of their reactivity towards NADPH:cytochrome P-450 reductase and and Plasmodium falciparum ferredoxin:NADP+ oxidoreductase, and with their reactivity towards rat NQO1
evolution
chicken POR shares high homology with other vertebrates PORs and possesses the conserved binding domains of FAD, FMN, and NADPH
evolution
grouping of dual Cytochrome P450 reductases, CPRs, is in accordance with class I and class II of eudicotyledon CPRs, overview
evolution
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Spodoptera littoralis P450s belong to four clades defined by their conservation with vertebrate P450s and their cellular localization
evolution
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the enzyme is a member of the diflavin oxidoreductase family. They are multi-domain enzymes containing distinct FAD and FMN domains connected by a flexible hinge. The protein has evolved by fusing two ancestral genes that encode proteins related to a FMN-containing flavodoxin and a FAD-containing ferredoxin-NADP+ oxidoreductase
evolution
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the enzyme is a member of the diflavin oxidoreductase family. They are multi-domain enzymes containing distinct FAD and FMN domains connected by a flexible hinge. The protein has evolved by fusing two ancestral genes that encode proteins related to a FMN-containing flavodoxin and a FAD-containing ferredoxin-NADP+ oxidoreductase
malfunction
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mutations in POR may reduce heme oxygenase-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles
malfunction
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human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like syndrome, ABS
malfunction
the down-regulation of enzyme contributes to an increase of the susceptibility to fenpropathrin in resistant mites
metabolism
human P450 1A2 and 2A6 are able to successfully catalyze the O-deethylation of 7-ethoxyresorufin and the 7-hydroxylation of coumarin, respectively, with the support of the purified enzyme NPR. Purified NPR is an orthologous reductase protein that supports cytochrome P450 enzymes in Malassezia globosa
metabolism
involvement of the enzyme in the withanolide biosynthesic pathway, overview
metabolism
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microsomal P450 systems, overview
metabolism
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microsomal P450 systems, overview
metabolism
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the enzyme enhances H-rev107-mediated amino acid release
metabolism
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the enzyme functions as a redox partner for sterol 14alpha-demethylase CYP51
metabolism
salt dependency of either cytochrome c or P450 reductions can be mostly attributed to a change in the conformational equilibrium of CPR. In the membrane bound form of wild-type CPR, the kobs value is lower than the one measured with the soluble form
metabolism
upon cryo-reduction of oxidized yeast CPR containing an equimolar ratio of both FAD and FMN, or FAD alone, neutral semiquinones are trapped at 77 K. During annealing at the elevated temperatures, unstable short-lived neutral semiquinones relax to spectroscopically distinct air-stable neutral semiquinones. This transition is independent of pH within the 6.0-10.7 range
metabolism
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upon cryo-reduction of oxidized yeast CPR containing an equimolar ratio of both FAD and FMN, or FAD alone, neutral semiquinones are trapped at 77 K. During annealing at the elevated temperatures, unstable short-lived neutral semiquinones relax to spectroscopically distinct air-stable neutral semiquinones. This transition is independent of pH within the 6.0-10.7 range
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physiological function
the recombinant enzymes supports the activity of CYP73A25, a cinnamate 4-hydroxylase of cotton
physiological function
CYPOR is an essential electron donor to microsomal P450s, therefore it is critical to the function of the large number of physiologic processes regulated by P450
physiological function
cytochrome P450 reductase is the most imperative redox partner of multiple P450s involved in primary and secondary metabolite biosynthesis
physiological function
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NADPH-cytochrome P450 reductase is essential for the functioning of microsomal cytochrome P450 monooxygenases and heme oxygenases. Potential biological functions of cytochrome P450 reductase-dependent enzymes in small intestine in expression of major histocompatibility complex class II genes
physiological function
NADPH-cytochrome P450 reductase is one of the most important components of the cytochrome P450 enzyme system. It catalyzes electron transfer from NADPH to all known P450s, thus plays central roles not only in the metabolism of exogenous xenobiotics but also in the regulation of endogenous hormones in insects
physiological function
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regulation of gap junction function by CYPOR, Cx43 may play an important role(s) in CYPOR-mediated bone defects
physiological function
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regulation of gap junction function by CYPOR, Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients
physiological function
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regulation of the CPR gene by odorants within insect antennae
physiological function
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the enzyme is capable of activating molecular oxygen on its own merit, generating diffusible reduced oxygen species. It deplete peroxide via diffusible radical mediated process, thereby leading to the formation of water (but without significant evolution of oxygen). CPR mediated processes are bound to be energetically wasteful and potentially hazardous owing to the unavoidable nature of the CPR to generate and deplete diffusible reduced oxygen species. Molecular mechanisms of oxygen activation and peroxide depletion by CPR, overview
physiological function
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CYP76F45 and NADPH-cytochrome P450 reductase CPR I function as the enzyme geraniol-8-hydroxylase, which is likely to be involved in the biosynthesis of the indole alkaloid in Croton stellatopilosus
physiological function
the enzyme is important for the development of Helicoverpa armigera and may play an essential role in the P450-mediated insecticide resistance of Helicoverpa armigera to fenvalerate
physiological function
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the enzyme plays an important role in regulating all-trans-retinoic acid efficacy and CYP26A1 expression in HL-60 cells
physiological function
the enzyme plays an important role in the P450-mediated insecticide resistance of Rhopalosiphum padi to isoprocarb and imidacloprid
physiological function
coexpression of CPR and P450 cytochromes CYP6AE14 or CYP9A12 of Helicoverpa armigera in Pichia pastoris. CYP6AE14 is not involved in gossipol degradation, but CYP9A12 takes part in gossipol metabolism
physiological function
CPR1 supports CYP76AH1 monooxygenase activity upon expression in yeast
physiological function
downregulation of CPR via RNAi leads to reduced enzymatic activities of CPR and cytochrome P450s, as well as a reduction of resistance to multiple acaricides, abamectin, bifenthrin, and fenpyroximate
physiological function
enzyme successfully supports the catalytic activities of human P450 1A2 and 2A6 and fungal CYP52A21
physiological function
identification of 2 transcripts CPR-X1 and CPR-X2. The deduced protein of CPR-X1 contains all features (N-terminal membrane anchor, FMN, FAD and NADP binding domains, FAD binding motif, and catalytic residues). No N-terminal member anchor and a shorter FMN binding region have been identified in the deduced protein of CPR-X2. SPR-X1 with the N-terminal membrane anchor is the major CPR potentially involved in Spodoptera litura indoxacarb resistance
physiological function
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squalene epoxidase catalyzes the epoxidation of squalene in coordination with NADPH-cytochrome P450 reductase CPR. When squalene epoxidase and CPR are incubated with the substrates squalene and NADPH, 2,3-oxidosqualene is formed as the product
additional information
CPR is a diflavin protein containing the flavin cofactors FAD, accepting hydride ions from NADPH, and FMN, accepting single electrons from FAD and reducing the heme center of the P450 monooxygenase domain
additional information
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CPR is a diflavin protein containing the flavin cofactors FAD, accepting hydride ions from NADPH, and FMN, accepting single electrons from FAD and reducing the heme center of the P450 monooxygenase domain
additional information
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cytochrome P450 reductase is a membrane-bound diflavin protein, which transfers two electrons sequentially from NADPH through FAD to the FMN cofactor, which is the ultimate donor of electrons to cytochrome P450 and other acceptor proteins
additional information
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FAD accepts a hydride ion from NADPH, and reduced FAD donates electrons to FMN, which in turn transfers electrons to the heme center of cytochrome P450 or NOS oxygenase domain, electron transfer mechanism, overview. The two flavin domains undergo large domain movements during catalysis, domain-domain interactions, structure-activity analysis, overview
additional information
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FAD accepts a hydride ion from NADPH, and reduced FAD donates electrons to FMN, which in turn transfers electrons to the heme center of cytochrome P450 oxygenase domain, electron transfer mechanism, overview. The two flavin domains undergo large domain movements during catalysis, domain-domain interactions, structure-activity analysis, overview
additional information
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interaction analysis of membrane-located enzyme CPR with cytochrome P450 CYP1A2, overview
additional information
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role of P450 hydrophobic residues in complex formation with CPR and uncovered novel roles for the surface-exposed residues V267 and L270 of CYP2B4 in mediating CYP2B4-CPR interactions, interaction analysis of wild-type and genetically engineered variants of cytochrome c CYP2B4, i.e. V267C, L270C, L420C, R133C, Y484C, H226C or E60C., overview
additional information
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the antennae of insects are a key site for P450-mediated metabolism of a large range of exogenous and endogenous molecules
additional information
the electron transfer pathway in CYPOR begins with the obligate two electron donor, NADPH, which transfers a hydride ion to FAD, which in turn donates electrons to the FMN cofactor. The FMN hydroquinone then transfers electrons, one at a time, to its redox partners. Comparison of the structures without and with NADP+ shows movement of the Gly631-Asn635 loop. In the NADP+-free structure, the loop adopts a conformation that sterically hinders NADP(H) binding. The structure with NADP+ shows movement of the Gly631-Asn635 loop to a position that permits NADP(H) binding. Comparison of mutant and wild-type structures, overview. The Gly631-Asn635 loop movement controls NADPH binding and NADP+ release, this loop movement in turn facilitates the flavin domain movement, allowing electron transfer from FMN to the CYPOR redox partners
additional information
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CPR is a diflavin protein containing the flavin cofactors FAD, accepting hydride ions from NADPH, and FMN, accepting single electrons from FAD and reducing the heme center of the P450 monooxygenase domain
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