Cholesterol side-chain cleavage enzyme, mitochondrial

UniProt P05108 Organism Homo sapiens Gene CYP11A, CYP11A1 EC 1.14.15.6

Also known as: CYP11A, CYP11A1

Function

A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal. 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).

Classification

Family (Pfam): PF00067 p450
InterPro: CYP11_CYP27_families, Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf
Functional cluster: Zinc-Finger & Ubiquitination Proteins

Experimental structures · PDB · 4

3N9Y X-ray 2.10A
3N9Z X-ray 2.17A
3NA0 X-ray 2.50A
3NA1 X-ray 2.25A

A predicted model is available from AlphaFold.

Gene Ontology · 14

Disease associations

Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency MONDO:0013400

Drugs targeting this protein · 3

MITOTANE inhibitor
LEVOKETOCONAZOLE inhibitor
AMINOGLUTETHIMIDE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Adrenodoxin, mitochondrial 1 shared papers

Literature · 14 cited papers

Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc. Natl. Acad. Sci. U.S.A. · 2011
A novel homozygous mutation in CYP11A1 gene is associated with late-onset adrenal insufficiency and hypospadias in a 46,XY patient. J. Clin. Endocrinol. Metab. · 2009
Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc. J. Clin. Endocrinol. Metab. · 2008
Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum. J. Clin. Endocrinol. Metab. · 2006
Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans. J. Clin. Endocrinol. Metab. · 2002
Heterozygous mutation in the cholesterol side chain cleavage enzyme (P450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency. J. Clin. Endocrinol. Metab. · 2001
Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet. · 1999
Gene structure of human cytochrome P-450(SCC), cholesterol desmolase. J. Biochem. · 1987
Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc. Natl. Acad. Sci. U.S.A. · 1986
… and 2 more in the literature graph

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