Cytochrome P450 11B2, mitochondrial
Also known as: CYP11B2
Function
A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure. Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone (21-hydroxyprogesterone), namely 11-beta hydroxylation, followed by two successive oxidations at C18 yielding 18-hydroxy and then 18-oxo intermediates (that would not leave the enzyme active site during the consecutive hydroxylation reactions), ending with the formation of aldosterone. Can also produce 18-hydroxycortisol and 18-oxocortisol, derived from successive oxidations of cortisol at C18, normally found at very low levels, but significantly increased in primary aldosteronism, the most common form of secondary hypertension. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin). Besides its role in the biosynthesis of mineralocorticoids and glucocorticoids, it can also participate in the androgen metabolic pathway, converting testosterone (17beta-hydroxy-4-androsten-3-one) to 11beta,17beta-dihydroxyandrost-4-ene-3-one. Can also use progesterone as substrate.
Classification
- Family (Pfam)
- PF00067 p450
- InterPro
- CYP11_CYP27_families, Cyt_P450, Cyt_P450_CS, Cyt_P450_mitochondrial, Cyt_P450_sf
- Functional cluster
- Membrane Channels & Lipid-Anchored Proteins
Experimental structures · PDB · 7
- 4DVQ X-ray 2.49A
- 4FDH X-ray 2.71A
- 4ZGX X-ray 3.20A
- 6XZ8 X-ray 3.00A
- 6XZ9 X-ray 2.77A
- 7M8I X-ray 2.94A
- 7M8V X-ray 3.08A
A predicted model is available from AlphaFold.
Gene Ontology · 22
- GO:0005743 mitochondrial inner membrane
- GO:0005739 mitochondrion
- GO:0047783 corticosterone 18-monooxygenase activity
- GO:0020037 heme binding
- GO:0005506 iron ion binding
- GO:0004507 steroid 11-beta-monooxygenase activity
- GO:0008395 steroid hydroxylase activity
- GO:0032342 aldosterone biosynthetic process
- GO:0006700 C21-steroid hormone biosynthetic process
- GO:0032870 cellular response to hormone stimulus
- GO:0071375 cellular response to peptide hormone stimulus
- GO:0035865 cellular response to potassium ion
- GO:0008203 cholesterol metabolic process
- GO:0034651 cortisol biosynthetic process
- GO:0034650 cortisol metabolic process
- GO:0006704 glucocorticoid biosynthetic process
- GO:0006705 mineralocorticoid biosynthetic process
- GO:0055075 potassium ion homeostasis
- GO:0002017 regulation of blood volume by renal aldosterone
- GO:0003091 renal water homeostasis
- GO:0055078 sodium ion homeostasis
- GO:0016125 sterol metabolic process
Disease associations
- corticosterone methyloxidase type 1 deficiency MONDO:0008751
- corticosterone methyloxidase type 2 deficiency MONDO:0012524
Drugs targeting this protein · 1
- LEVOKETOCONAZOLE inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Cytochrome P450 11B1, mitochondrial 0.99
- Cytochrome P450 11B1, mitochondrial 0.99
- Cytochrome P450 11B1, mitochondrial 0.97
- Cytochrome P450 11B1, mitochondrial 0.97
- Cytochrome P450 11B1, mitochondrial 0.96
- Cytochrome P450 11B3, mitochondrial 0.94
- Cytochrome P450 11B2, mitochondrial 0.93
- Cytochrome P450 11B2, mitochondrial 0.93
- Cytochrome P450 11B2, mitochondrial 0.92
- Cytochrome P450 11B1, mitochondrial 0.90
- Cytochrome P450 11B1, mitochondrial 0.87
- Cholesterol side-chain cleavage enzyme, mitochondrial 0.84
Co-cited proteins · studied together in the literature
- Cytochrome P450 11B1, mitochondrial 8 shared papers
- 3-oxo-5-alpha-steroid 4-dehydrogenase 2 1 shared papers
- 3-oxo-5-alpha-steroid 4-dehydrogenase 1 1 shared papers
- 11-beta-hydroxysteroid dehydrogenase type 2 1 shared papers
- 11-beta-hydroxysteroid dehydrogenase 1 1 shared papers
- Apolipoprotein A-IV 1 shared papers
- Dopamine beta-hydroxylase 1 shared papers
- Thromboxane-A synthase 1 shared papers
- Apolipoprotein C-II 1 shared papers
- Alpha-adducin 1 shared papers
- Apolipoprotein C-I 1 shared papers
- Beta-3 adrenergic receptor 1 shared papers
Literature · 26 cited papers
- Characterization of human adrenal cytochrome P450 11B2 products of progesterone and androstenedione oxidation. J. Steroid Biochem. Mol. Biol. · 2021
- 11beta-hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5alpha-reductase yielding 11beta-hydroxy-5alpha-androstanedione. J. Steroid Biochem. Mol. Biol. · 2013
- Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol. Endocrinol. · 2013
- Human aldosterone synthase: recombinant expression in E. coli and purification enables a detailed biochemical analysis of the protein on the molecular level. J. Steroid Biochem. Mol. Biol. · 2012
- Adrenocortical zonation in humans under normal and pathological conditions. J. Clin. Endocrinol. Metab. · 2010
- Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol in normal human subjects. J. Clin. Endocrinol. Metab. · 2004
- A compound heterozygote case of type II aldosterone synthase deficiency. J. Clin. Endocrinol. Metab. · 2003
- Modulation of steroid hydroxylase activity in stably transfected V79MZh11B1 and V79MZh11B2 cells by PKC and PKD inhibitors. Endocr. Res. · 2002
- The effect of amino-acid substitutions I112P, D147E and K152N in CYP11B2 on the catalytic activities of the enzyme. Eur. J. Biochem. · 2002
- Type 1 aldosterone synthase deficiency presenting in a middle-aged man. J. Clin. Endocrinol. Metab. · 2001
- Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat. Genet. · 1999
- Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet. · 1999
- … and 14 more in the literature graph