Cytochrome P450 2B6

Function

A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling. Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2. Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs. Acts as a 1,4-cineole 2-exo-monooxygenase.

Classification

Family (Pfam)

PF00067 p450

InterPro

Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_E_grp-I_CYP2B-like, Cyt_P450_sf, Cytochrome_P450_fam2

Functional cluster

Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 13

• 3IBD X-ray 2.00A
• 3QOA X-ray 2.10A
• 3QU8 X-ray 2.80A
• 3UA5 X-ray 2.80A
• 4I91 X-ray 2.00A
• 4RQL X-ray 2.10A
• 4RRT X-ray 2.20A
• 4ZV8 X-ray 2.24A
• 5UAP X-ray 2.03A
• 5UDA X-ray 1.93A
• 5UEC X-ray 2.27A
• 5UFG X-ray 1.76A
• … and 1 more

A predicted model is available from AlphaFold.

Gene Ontology · 18

• GO:0005737 cytoplasm
• GO:0005789 endoplasmic reticulum membrane
• GO:0062188 anandamide 11,12 epoxidase activity
• GO:0062189 anandamide 14,15 epoxidase activity
• GO:0062187 anandamide 8,9 epoxidase activity
• GO:0008392 arachidonate epoxygenase activity
• GO:0101021 estrogen 2-hydroxylase activity
• GO:0020037 heme binding
• GO:0005506 iron ion binding
• GO:0004497 monooxygenase 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
• GO:0008390 testosterone 16-alpha-hydroxylase activity
• GO:0062184 testosterone 16-beta-hydroxylase activity
• GO:0019373 epoxygenase P450 pathway
• GO:0042180 ketone metabolic process
• GO:0008202 steroid metabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0006805 xenobiotic metabolic process

Disease associations

• obsolete efavirenz, poor metabolism of MONDO:0013799

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Cytochrome P450 2B1 0.98
• Cytochrome P450 2B2 0.98
• Cytochrome P450 2B11 0.98
• Cytochrome P450 2B4 0.98
• Cytochrome P450 2B5 0.98
• Cytochrome P450 2B19 0.98
• Cytochrome P450 2B9 0.98
• Cytochrome P450 2B12 0.97
• Cytochrome P450 2B10 0.97
• Cytochrome P450 2F3 0.97
• Cytochrome P450 2B15 0.97
• Cytochrome P450 2F2 0.97

Co-cited proteins · studied together in the literature

• Cytochrome P450 2D6 2 shared papers
• Cytochrome P450 2A6 3 shared papers
• Cytochrome P450 3A4 3 shared papers
• S-formylglutathione hydrolase 1 shared papers
• Cytochrome P450 3A5 2 shared papers
• Arylacetamide deacetylase 1 shared papers
• Cytochrome P450 7A1 1 shared papers
• Cytochrome P450 2C9 2 shared papers
• Cytochrome P450 2A13 1 shared papers
• Cocaine esterase 1 shared papers
• Thromboxane-A synthase 1 shared papers
• Cytochrome P450 3A7 1 shared papers

Literature · 23 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Conformational adaptation of human cytochrome P450 2B6 and rabbit cytochrome P450 2B4 revealed upon binding multiple amlodipine molecules. Biochemistry · 2012
• Structures of cytochrome P450 2B6 bound to 4-benzylpyridine and 4-(4-nitrobenzyl)pyridine: insight into inhibitor binding and rearrangement of active site side chains. Mol. Pharmacol. · 2011
• Anandamide oxidation by wild-type and polymorphically expressed CYP2B6 and CYP2D6. Drug Metab. Dispos. · 2011
• Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients. Pharmacogenomics · 2010
• Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort. J. Antimicrob. Chemother. · 2010
• Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution. Mol. Pharmacol. · 2010
• Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS · 2004
• Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics · 2004
• Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem. Biophys. Res. Commun. · 2004
• Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J. Pharmacol. Exp. Ther. · 2004
• The DNA sequence and biology of human chromosome 19. Nature · 2004
• … and 11 more in the literature graph