Cytochrome P450 11B1, mitochondrial

UniProt P15538 Organism Homo sapiens Gene CYP11B1, S11BH EC 1.14.15.4

Also known as: CYP11B1, S11BH

Function

A cytochrome P450 monooxygenase mainly involved in the biosynthesis of adrenal corticoids. Catalyzes a variety of reactions that are essential for many species, including detoxification, defense, and the formation of endogenous chemicals like steroid hormones. Steroid 11beta, 18- and 19-hydroxylase with preferred regioselectivity at 11beta, then 18, and lastly 19 (By similarity). Catalyzes the hydroxylation of 11-deoxycortisol and 11-deoxycorticosterone (21-hydroxyprogesterone) at 11beta position, yielding cortisol or corticosterone, respectively, but cannot produce aldosterone. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate for hydroxylation 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). Due to its lack of 18-oxidation activity, it is incapable of generating aldosterone. Besides its role in the biosynthesis of mineralocorticoids and glucocorticoids, it can also participate in the androgen metabolic pathway, converting androst-4-ene-3,17-dione to 11beta-hydroxyandrost-4-ene-3,17-dione, and testosterone (17beta-hydroxy-4-androsten-3-one) to 11beta,17beta-dihydroxyandrost-4-ene-3-one.

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 · 2

6M7X X-ray 2.10A
7E7F X-ray 1.40A

A predicted model is available from AlphaFold.

Gene Ontology · 19

Disease associations

glucocorticoid-remediable aldosteronism MONDO:0007080
congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency MONDO:0008729

Drugs targeting this protein · 4

MITOTANE inhibitor
LEVOKETOCONAZOLE inhibitor
OSILODROSTAT PHOSPHATE inhibitor
METYRAPONE inhibitor

Neighborhood · nearest proteins

Nearest neighbours of Cytochrome P450 11B1, mitochondrial: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Cytochrome P450 11B2, mitochondrial 8 shared papers
Cytochrome P450 11B1, mitochondrial 1 shared papers
Steroid 21-hydroxylase 1 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

Literature · 30 cited papers

The in vitro metabolism of 11beta-hydroxyprogesterone and 11-ketoprogesterone to 11-ketodihydrotestosterone in the backdoor pathway. J. Steroid Biochem. Mol. Biol. · 2018
Phenotypic, metabolic, and molecular genetic characterization of six patients with congenital adrenal hyperplasia caused by novel mutations in the CYP11B1 gene. J. Steroid Biochem. Mol. Biol. · 2016
Characterization of the molecular genetic pathology in patients with 11beta-hydroxylase deficiency. Clin. Endocrinol. (Oxf.) · 2015
Two novel CYP11B1 gene mutations in patients from two Croatian families with 11 beta-hydroxylase deficiency. Int. J. Endocrinol. · 2014
Characterisation of three novel CYP11B1 mutations in classic and non-classic 11beta-hydroxylase deficiency. Eur. J. Endocrinol. · 2014
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional consequences of four CYP11B1 mutations. Eur. J. Hum. Genet. · 2014
A diagnosis not to be missed: nonclassic steroid 11beta-hydroxylase deficiency presenting with premature adrenarche and hirsutism. J. Clin. Endocrinol. Metab. · 2013
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
Novel homozygous p.R454C mutation in the CYP11B1 gene leads to 11beta-hydroxylase deficiency in a Chinese patient. Fertil. Steril. · 2011
Only two mutations detected in 15 Tunisian patients with 11beta-hydroxylase deficiency: the p.Q356X and the novel p.G379V. Clin. Genet. · 2010
Adrenocortical zonation in humans under normal and pathological conditions. J. Clin. Endocrinol. Metab. · 2010
… and 18 more in the literature graph

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