Bifunctional cytochrome P450/NADPH--P450 reductase

Function

Functions as a fatty acid monooxygenase. Catalyzes hydroxylation of fatty acids at omega-1, omega-2 and omega-3 positions. Shows activity toward medium and long-chain fatty acids, with optimum chain lengths of 12, 14 and 16 carbons (lauric, myristic, and palmitic acids). Able to metabolize some of these primary metabolites to secondary and tertiary products. Marginal activity towards short chain lengths of 8-10 carbons. Hydroxylates highly branched fatty acids, which play an essential role in membrane fluidity regulation. Also displays a NADPH-dependent reductase activity in the C-terminal domain, which allows electron transfer from NADPH to the heme iron of the cytochrome P450 N-terminal domain. Involved in inactivation of quorum sensing signals of other competing bacteria by oxidazing efficiently acyl homoserine lactones (AHLs), molecules involved in quorum sensing signaling pathways, and their lactonolysis products acyl homoserines (AHs).

Classification

Family (Pfam)

PF00667 FAD_binding_1, PF00258 Flavodoxin_1, PF00175 NAD_binding_1, PF00067 p450

InterPro

Bifunctional_P450_P450_red, CysJ-like_FAD-binding, Cyt_P450, Cyt_P450_CS, Cyt_P450_sf, FAD-bd_FR_type, Flavdoxin-like, Flavodoxin/NO_synth, Flavoprot_Pyr_Nucl_cyt_Rdtase, Flavoprotein-like_sf, FNR_nucleotide-bd, NADPH_Cyt_P450_Rdtase_alpha, OxRdtase_FAD/NAD-bd, Riboflavin_synthase-like_b-brl

Functional cluster

Mur-Ligase Peptidoglycan Biosynthesis Enzymes

Experimental structures · PDB · 188

• 1BU7 X-ray 1.65A
• 1BVY X-ray 2.03A
• 1FAG X-ray 2.70A
• 1FAH X-ray 2.30A
• 1JME X-ray 2.00A
• 1JPZ X-ray 1.65A
• 1P0V X-ray 2.05A
• 1P0W X-ray 2.00A
• 1P0X X-ray 2.00A
• 1SMI X-ray 2.00A
• 1SMJ X-ray 2.75A
• 1YQO X-ray 1.90A
• … and 176 more

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0005829 cytosol
• GO:0070330 aromatase activity
• GO:0050660 flavin adenine dinucleotide binding
• GO:0010181 FMN binding
• GO:0020037 heme binding
• GO:0042802 identical protein binding
• GO:0005506 iron ion binding
• GO:0003958 NADPH-hemoprotein reductase activity
• GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Bifunctional cytochrome P450/NADPH--P450 reductase 2 0.89
• Bifunctional cytochrome P450/NADPH--P450 reductase 0.84
• Bifunctional cytochrome P450/NADPH--P450 reductase 1 0.81
• Bifunctional cytochrome P450/NADPH--P450 reductase 0.67
• Sulfite reductase [NADPH] flavoprotein alpha-component 0.65
• Bifunctional cytochrome P450/NADPH--P450 reductase ascE 0.64
• Sulfite reductase [NADPH] flavoprotein alpha-component 0.64
• Self-sufficient cytochrome P450 monooxygenase CYP505U2 0.62
• Sulfite reductase [NADPH] flavoprotein alpha-component 0.61
• Self-sufficient cytochrome P450 monooxygenase CYP505E4 0.61
• Sulfite reductase [NADPH] flavoprotein alpha-component 0.61
• Self-sufficient cytochrome P450 monooxygenase CYP505E3 0.60

Co-cited proteins · studied together in the literature

• HTH-type transcriptional repressor Bm3R1 2 shared papers

Literature · 29 cited papers

• Complete genome sequences for 35 biothreat assay-relevant bacillus species. Genome Announc. · 2015
• A single active-site mutation of P450BM-3 dramatically enhances substrate binding and rate of product formation. Biochemistry · 2011
• Structural basis for the properties of two single-site proline mutants of CYP102A1 (P450BM3). ChemBioChem · 2010
• Photooxidation of cytochrome P450-BM3. Proc. Natl. Acad. Sci. U.S.A. · 2010
• Glutamate-haem ester bond formation is disfavoured in flavocytochrome P450 BM3: characterization of glutamate substitution mutants at the haem site of P450 BM3. Biochem. J. · 2010
• A highly active single-mutation variant of P450BM3 (CYP102A1). ChemBioChem · 2009
• Novel haem co-ordination variants of flavocytochrome P450BM3. Biochem. J. · 2009
• Evolutionary history of a specialized p450 propane monooxygenase. J. Mol. Biol. · 2008
• Crystal structure of inhibitor-bound P450BM-3 reveals open conformation of substrate access channel. Biochemistry · 2008
• Bacillus megaterium CYP102A1 oxidation of acyl homoserine lactones and acyl homoserines. Biochemistry · 2007
• Interactions of substrates at the surface of P450s can greatly enhance substrate potency. Biochemistry · 2007
• Filling a hole in cytochrome P450 BM3 improves substrate binding and catalytic efficiency. J. Mol. Biol. · 2007
• … and 17 more in the literature graph