Information on EC 1.14.15.6 - cholesterol monooxygenase (side-chain-cleaving)

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
1.14.15.6
-
RECOMMENDED NAME
GeneOntology No.
cholesterol monooxygenase (side-chain-cleaving)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
(1c)
-
-
-
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
(1b)
-
-
-
cholesterol + 2 reduced adrenodoxin + O2 = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
(1a)
-
-
-
cholesterol + 6 reduced adrenodoxin + 3 O2 = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
overall reaction
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Metabolic pathways
-
pregnenolone biosynthesis
-
Steroid hormone biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
cholesterol,reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving)
A heme-thiolate protein (cytochrome P-450). The reaction proceeds in three stages, with two hydroxylations at C-22 and C-20 preceding scission of the side-chain between carbons 20 and 22. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C27-side chain cleavage enzyme
-
-
-
-
cholesterol 20-22-desmolase
-
-
-
-
cholesterol C20-22 desmolase
-
-
-
-
cholesterol C20-C22 lyase
-
-
-
-
cholesterol desmolase
-
-
-
-
cholesterol hydroxylase
-
-
cholesterol side chain cleavage cytochrome P450
-
-
cholesterol side chain cleavage enzyme
P00189
-
cholesterol side chain cleavage enzyme
-
-
cholesterol side chain cleavage enzyme
P05108
-
cholesterol side chain cleavage enzyme
-
-
cholesterol side-chain cleavage cytochrome P450
Q4KYY5
-
cholesterol side-chain cleavage cytochrome P450 enzyme
-
-
cholesterol side-chain cleavage enzyme
-
-
-
-
cholesterol side-chain cleavage enzyme
-
-
cholesterol side-chain cleavage enzyme
-
-
cholesterol side-chain-cleaving enzyme
-
-
-
-
cholesterol side-cleaving enzyme
-
-
Cyp11a
-
-
CYP11A1
Q4KYY5
-
CYP11A1
P00189
-
CYP11A1
Rattus norvegicus Wistar
-
-
-
CYPXIA1
-
-
-
-
cytochrome P-450scc
-
-
-
-
cytochrome P450 11A1
P00189
-
cytochrome P450 cholesterol side chain cleavage
-
-
cytochrome P450 cholesterol side chain cleavage
-
-
cytochrome P450 cholesterol side-chain cleavage
Q4KYY5
-
cytochrome P450 side chain cleavage enzyme
-
-
cytochrome P450 side chain cleavage enzyme
Rattus norvegicus Wistar
-
-
-
cytochrome P450-mediated cholesterol side-chain cleavage enzyme
-
-
cytochrome P450-mediated side-chain cleavage enzyme
-
-
cytochrome P450scc
-
-
cytochrome P450scc
-
-
cytochrome P450scc
P05108
-
cytochrome P450scc
-
-
desmolase, steroid 20-22
-
-
-
-
endoenzymes, cholesterol side-chain-cleaving
-
-
-
-
enzymes, cholesterol side-chain-cleaving
-
-
-
-
P450 11A1
P00189
-
P450 cholesterol side-chain cleavage enzyme
-
-
P450 cholesterol side-chain cleavage enzyme
-
-
P450 cholesterol side-chain cleavage enzyme
-
-
P450 cholesterol side-chain cleavage enzyme
-
-
P450 cholesterol side-chain cleavage enzyme
-
-
P450(scc)
-
-
-
-
P450scc
Q4KYY5
-
P450scc
-
-
P450scc
-
-
P450scc
-
-
P450scc
-
-
P450scc
P05108
-
P450scc
-
-
P450scc
-
-
P450scc
-
-
steroid 20-22 desmolase
-
-
-
-
steroid 20-22-lyase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37292-81-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
yellowtail clownfish, an protandrous hemaphroditic, anemone-symbiontic fish
-
-
Manually annotated by BRENDA team
Japanese eel, gene CYP11A1
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
enzyme incorporated into phosphatidylcholine vesicles
-
-
Manually annotated by BRENDA team
female
-
-
Manually annotated by BRENDA team
fusion protein with adrenodoxin and/or adrenodoxin reductase
-
-
Manually annotated by BRENDA team
hircus
-
-
Manually annotated by BRENDA team
non-breeding male
-
-
Manually annotated by BRENDA team
fusion protein with adrenodoxin and/or adrenodoxin reductase
-
-
Manually annotated by BRENDA team
gene CYP11A1
-
-
Manually annotated by BRENDA team
gene CYP11A1
UniProt
Manually annotated by BRENDA team
gene p450scc
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
waterborne nonylphenol-treated juvenile Atlantic salmon
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
conversion of cholesterol to pregnenolone by P450scc represents the initiation of steroidogenesis
metabolism
-
vitamin D2 metabolism occurs with lower efficiency than that observed for both cholesterol and D3 metabolism by P450scc
metabolism
-
CYP11A1 is a Runx2-responsive gene and may represent an integral component of a biological program that is controlled by Runx2 to regulate enzymes mediating sterol/steroid metabolism
physiological function
-
endocrine disrupting chemical modulation of acute steroid hormone regulation by targeting StAR and P450scc may have severe consequences for the entire reproduction process, including oocyte growth, development and overt fecundity
physiological function
-
expression of StAR and P450scc transcripts is related to steroid synthesis
physiological function
-
Escherichia coli membrane interacting peptides in CYP11A1 are from the putative F-G loop (residues 218-225) and the C-terminal portion of the G helix (residues 238-250)
physiological function
-
CYP11A1 suppresses osteoblast proliferation, specific CYP11A1 knockdown with short hairpin RNA increases cell proliferation
physiological function
D0EFX3, -
the enzyme shows steroidogenic activity. The stress peptide adrenocorticotropic hormone, ACTH, elicits its effects on corticosteroidogenesis in part through regulation of StAR and P450scc mRNAs. Chronic ACTH-induced glucocorticoid synthesis in elasmobranchs is mediated by regulation of primary steroidogenic mRNAs
physiological function
-
cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3. It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone, which can be transformed to 20-hydroxy-7-dehydropregnenolone. The secosteroids inhibit proliferation and induce erythroid differentiation of diverse leukemic cells, and are only slightly less potent than 1,25-dihydroxy-vitamin D3, but show no or lower calcemic activity compared to 1,25-dihydroxy-vitamin D3, molecular modeling, overview
metabolism
-
Cyp11a is responsible for the first step in steroidogenesis, catalyzing the conversion of cholesterol to prognenolone
additional information
P00189
the active site cavity in CYP11A1 represents a long curved tube that extends from the protein surface to the heme group, the site of catalysis. Shuttling of the sterol intermediates between the active site entrance and the heme group during the three-step reaction. Structural basis of the strict substrate specificity and high catalytic efficiency of the enzyme, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
-
-
-
-
?
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
P00189
-
-
-
?
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
(20S)-22-thiacholesterol + reduced adrenodoxin + O2
(20S,22R)-22-thiacholesterol S-oxide + (20S,22S)-22-thiacholesterol S-oxide
show the reaction diagram
-
-
(22R)-sulfoxide preferentially formed by a factor of 4.2 to 1 over (22S)-sulfoxide
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
P00189
-, product binding structure analysis, detailed overview
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
17,20-dihydroxyvitamin D2 + reduced adrenodoxin + O2
17,20,24-trihydroxyvitamin D2 + oxidized adrenodoxin + O2
show the reaction diagram
-
is slowly metabolized
-
-
?
20,23-dihydroxyvitamin D3 + reduced adrenodoxin + O2
17,20,23-trihydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
20,23-dihydroxyvitamin D3 + reduced adrenodoxin + O2
17alpha,20,23-trihydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
20-hydroxyvitamin D2 + reduced adrenodoxin + O2
17,20,24-trihydroxyvitamin D2 + oxidized adrenodoxin + O2
show the reaction diagram
-
is a better substrate than vitamin D2 itself
-
-
?
20-hydroxyvitamin D3 + reduced adrenodoxin + O2
20,23-dihydroxyvitamin D3 + 17alpha,20,23-trihydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
20-hydroxyvitamin D3 + reduced adrenodoxin + O2
20,23-dihydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
20alpha, 22(R)-dihydroxycholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
20alpha-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
20alpha-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
22(R)-hydroxycholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
22(R)-hydroxycholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
show the reaction diagram
-
mitochondria containing the AAC-mCYP11A1 hybrid have the highest cholesterol side-chain cleavage activity in the reconstituted system. Ad-mCYP11A1 hybrid demonstrates only residual enzyme activity
-
-
?
22(R)-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxycholesterol + O2 + reduced ferredoxin
pregnenolone + H2O + ferredoxin + 4-hydroxy-4-methylpentanal
show the reaction diagram
-
-
-
-
?
25-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + oxidized adrenodoxin + H2O
show the reaction diagram
-, Q9EPT4
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
P00189
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
-
-
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
isocapraldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
isocapraldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
isocaproic aldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
P00189
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
Rattus norvegicus Wistar
-
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin mutant S112W + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin mutant S112W + 4 H2O
show the reaction diagram
-
overall reaction, adrenodoxin mutant S112W gives a 14fold higher catalytic efficiency compared to wild-type adrenodoxin
-
-
?
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin
show the reaction diagram
-
-, first and rate-limiting enzyme in adrenal steroidogenesis
-
-
?
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + adrenal ferredoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + adrenal ferredoxin + H2O
show the reaction diagram
P05108
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
isocaproaldehyde produced besides
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
intermediates (22R)-22-hydroxycholesterol and (20R,22R)-20,22-dihydroxycholesterol from hydroxylation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
intermediates (22R)-22-hydroxycholesterol and (20R,22R)-20,22-dihydroxycholesterol from hydroxylation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
20- or 22-hydroxycholesterol and 20,22-dehydroxycholesterol are putative intermediates
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
regioselective and stereospecific transformation, intermediates 22R-hydroxycholesterol and 20alpha,22R-dihydroxycholesterol from hydroxylation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
without demonstrable accumulation of putative intermediates 20alpha-hydroxycholesterol and 20alpha,22-dehydroxycholesterol
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
stable intermediates: 22-hydroxycholesterol and 20,22-dihydroxycholesterol
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
show the reaction diagram
-
hydroxylation of cholesterol at C-22, then C-20, followed by oxidative scission of the glycol to get pregnenolone
-
?
cholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
-
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
show the reaction diagram
-
-, metabolic regulation of enzyme expression, overview
-
-
?
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
show the reaction diagram
-
the catalyzed reaction is not the rate-limiting step in steroidogenesis except in placenta which lacks the steroidogenic acute regulatory protein, overview, enzyme deficiency by mutations leads to severe disorders, overview, the enzyme is a cytochrome P450 enzyme, the enzyme structure possesses a substrate access channel, which is responsible for regioselectivity of the enzyme together with residue F202
-
-
?
vitamin D2 + reduced adrenodoxin + O2
17,20,24-trihydroxyvitamin D2 + oxidized adrenodoxin + H2O
show the reaction diagram
-
P450scc catalyzes three sequential hydroxylations of D2 producing 20-hydroxyvitamin D2, 17,20-dihydroxyvitamin D2, and 17,20,24-trihydroxyvitamin D2, which dissociate from the active site of P450scc and accumulate in the reaction mixture
-
-
?
vitamin D3 + reduced adrenodoxin + O2
20-hydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
when incubated in 0.45% cyclodextrin, 20-hydroxyvitamin D3 is the major product of vitamin D3 metabolism by P450scc. The second major product is 20,23-dihydroxyvitamin D3. Major products dissociate from the P450scc active site and accumulate at a concentration well above the P450scc concentration
-
?
vitamin D3 + reduced adrenodoxin + O2
20-hydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
-
is hydroxylated with lower efficiency than cholesterol
-
-
?
cholesterol sulfate + reduced adrenodoxin + O2
pregnenolone sulfate + 17-hydroxy-pregnenolone + dehydroisoandrosterone sulfate + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
cholesterol side chain cleavage activity is dependent on free reduced adrenodoxin
-
-
-
additional information
?
-
-
one-enzyme-three-step hypothesis
-
-
-
additional information
?
-
-
21 amino-acid residues from Pro-8 to Arg-28 in the amino-terminus are located in or near the cholesterol-binding site, this site is in a quite different region from the adreno-ferredoxin binding site Pro374 to Iso-389
-
-
-
additional information
?
-
-
only a single active site of enzyme
-
-
-
additional information
?
-
-
electron shuttle between flavoprotein and cytochrome, biphasic reduction kinetics, rapid association of cytochrome and adrenodoxin, slower intracomplex electron transfer from iron-sulfur center of adrenodoxin to heme of cytochrome P-450scc
-
-
-
additional information
?
-
-
suggested shuttle mechanism in which adrenodoxin transfers electrons between adrenodoxin reductase and cytochrome P-450. No ternary adrenodoxin-adrenodoxin reductase-P-450 complex
-
-
-
additional information
?
-
-
transfer of cholesterol to cytochrome P-450scc is rate-limiting
-
-
-
additional information
?
-
-
3 high regioselective and stereospecific oxidation steps at the same heme active site
-
-
-
additional information
?
-
-
dissociation of oxidized adrenodoxin from P-450scc must be a potential rate-limiting factor
-
-
-
additional information
?
-
-
reduction of adrenodoxin must be rate-limiting step
-
-
-
additional information
?
-
-
2 interaction processes with 2 different sensitivities to ionic strength
-
-
-
additional information
?
-
-
involved in control of pain mechanisms
-
-
-
additional information
?
-
-
leptin interferes with adrenocorticotropin/cAMP signaling, possibly through a janus kinase 2-phosphatidylinositol 3-kinase/akt-phosphodiesterase 3-cAMP pathway, to down-regulate cholesterol side-chain cleavage cytochrome P450 enzyme in human adrenocortical NCI-H295 cell line, mechanism, overview
-
-
-
additional information
?
-
-
the enzyme is a key enzyme in brain steroidogenesis
-
-
-
additional information
?
-
-
the enzyme is important in steroidogenesis, regulatory mechanism, overview
-
-
-
additional information
?
-
-
cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3. It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone, which can be transformed to 20-hydroxy-7-dehydropregnenolone
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
-
-
-
-
?
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
P00189
-
-
-
?
(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
P00189
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
P00189
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
-
-
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
-
isocapraldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
isocapraldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
first step in biosynthesis of all steroid hormones
isocaproic aldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
-
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
P00189
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
show the reaction diagram
Rattus norvegicus Wistar
-
overall reaction
-
-
?
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin
show the reaction diagram
-
first and rate-limiting enzyme in adrenal steroidogenesis
-
-
?
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + adrenal ferredoxin + H2O
show the reaction diagram
-
-
-
-
?
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + adrenal ferredoxin + H2O
show the reaction diagram
P05108
-
-
-
?
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
show the reaction diagram
-
metabolic regulation of enzyme expression, overview
-
-
?
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
show the reaction diagram
-
the catalyzed reaction is not the rate-limiting step in steroidogenesis except in placenta which lacks the steroidogenic acute regulatory protein, overview, enzyme deficiency by mutations leads to severe disorders, overview
-
-
?
additional information
?
-
-
involved in control of pain mechanisms
-
-
-
additional information
?
-
-
leptin interferes with adrenocorticotropin/cAMP signaling, possibly through a janus kinase 2-phosphatidylinositol 3-kinase/akt-phosphodiesterase 3-cAMP pathway, to down-regulate cholesterol side-chain cleavage cytochrome P450 enzyme in human adrenocortical NCI-H295 cell line, mechanism, overview
-
-
-
additional information
?
-
-
the enzyme is a key enzyme in brain steroidogenesis
-
-
-
additional information
?
-
-
the enzyme is important in steroidogenesis, regulatory mechanism, overview
-
-
-
additional information
?
-
-
cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3. It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone, which can be transformed to 20-hydroxy-7-dehydropregnenolone
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
adrenodoxin
-
transports electrons from adrenodoxin reductase to cytochrome P-450 by shuttling
-
adrenodoxin
-
required
-
adrenodoxin
-
promotes cholesterol binding
-
adrenodoxin
-
electron shuttle
-
adrenodoxin
-
-
-
adrenodoxin
-
i.e. Adx , mechanism of the redox partner interactions, role of adrenodoxin electrostatic contributions, overview. Contruction of an Adx mutant lacking the C-terminal amino acids 113-128 and bearing a S112W point mutation, the mutant shows increased effciency towards CYP11A1-dependent cholesterol conversion. The complex between AdxS112W and CYP11A1 is about 4fold stronger than the respective complex with wild-type Adx, stopped flow kinetics, overview
-
adrenodoxin
-
-
-
cytochrome P450
-
-
-
cytochrome P450
-
-
-
cytochrome P450
-
-
-
cytochrome P450
-
-
-
Ferredoxin
-
-
-
Ferredoxin
-
-
-
Ferredoxin
-
-
-
heme
-
low heme content
heme
-
haemoprotein
heme
-
8 heme groups per molecule P-450
heme
-
0.78 heme group/unit of 48000 Da P-450, 1 mol of iron/44000 g
heme
-
3 mixed function oxidation cycles at the single heme center
heme
-
8 molecules of meme per molecule of enzyme
heme
-
content of 18.9 nmol/mg protein; hemeprotein
heme
P00189
site of catalysis
Iron
-
the enzyme is a cytochrome P450 enzyme
reduced adrenal ferredoxin
-
-
reduced adrenal ferredoxin
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
very little
Ca2+
-
ineffective activator; particulary but also other metal ions modulate adrenodoxin binding to adrenodoxin reductase and P-450, therefore activation of cholesterol side chain cleavage and adrenodoxin reduction
Ca2+
-
increased rate of association of cholesterol to partially purified cytochrome P-450scc
Fe2+
-
heme iron
Fe2+
P05108
a cytochrome P450 enzyme
Fe2+
-
cytochrome P450 enzyme
Fe2+
-
heme iron
Mg2+
-
-
Mg2+
-
increased MgCl2 concentrations continue to increase side chain cleavage activity even after all adrenodoxin is reduced
additional information
-
Kd for adrenodoxin increases with increase of ions from NaCl, binding of adrenodoxin to P-450scc is more sensitive to changes in metal ion concentration than cholesterol binding, high salt concentrations cause fall-off in activity
additional information
-
increase of side chain cleavage activity from 50 to 100 mM NaCl, higher concentrations cause a decrease, total loss at 300 mM
additional information
-
several cations and anions promote the dissociation of adrenodoxin-cytochrome P-450scc complex, decreasing order: K+, Cs+, Rb+, Na+, Li+ and SCN-, Br-, Cl-, respectively. The order for dissotiation of adrenodoxin-adrenodoxin reductase complex: Rb+, Cs+, K+, Li+, Na+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(20R,S)-20-amino-5-pregnen-3beta-ol
-
20-amine derivative, amine is attached closer to the D-ring than in the 22-amine, very weak inhibitor, 0.1 mM causes less than 20% inhibition
-
(20S)-22-thiacholesterol
-
competitive inhibitor, is converted enzymatically to a more potent inhibitor, the (22S) and (22R) sulfoxides, inhibition by approximately 75% at 0.001 mM, no inactivation in absence of NADPH and O2
(20S,22R)-22-thiacholesterol S-oxide
-
competitive versus cholesterol, binds 10times more tightly than (22S) diastereomer, 25% and 44% inhibition at 0.00005 mM and 0.0001 mM, respectively, complete inhibition at 0.001 mM, no substrate for P-450
(20S,22S)-22-thiacholesterol S-oxide
-
competitive versus cholesterol, no substrate for P-450
(22R)-22-Aminocholesterol
-
completely inhibited by 0.001 mM, affinity toward the P-450scc almost 3fold greater than that for the (22S) form, competitive versus cholesterol, no substrate for P-450
(22S)-22-Aminocholesterol
-
not inhibited below 0.001 mM, competitive versus cholesterol, no substrate for P-450
17,20-dihydroxyvitamin D2
-
competitive inhibitor
17beta-amino-5-androsten-3beta-ol
-
17-amine derivative, amine is attached closer to the D-ring than in the 22-amine, very weak inhibitor, 0.1 mM causes less than 20% inhibition
22-Amino-23,24-bisnor-5-cholen-3beta-ol
-
22-amine derivative, same steroid ring structure as cholesterol, competitive inhibitor with respect to cholesterol, 50% reversible inhibition at 0.0001 mM, reversible cooperative binding
22-Amino-23,24-bisnor-5-cholen-3beta-ol
-
22-amine derivative, same steroid ring structure as cholesterol, competitive inhibitor with respect to cholesterol, 50% reversible inhibition at 0.0001 mM, reversible cooperative binding; dual interaction: binding of steroid ring to cholesterol site and bonding of the amine to the heme iron. need not be metabolically activated in order to inhibit the enzyme, not metobolized to pregnenolone. 60% competitive inhibition at 0.00015 mM
22-amino-23,24-bisnor-5alpha-cholen-3beta-ol
-
50% inhibition at 0.003 mM
23,24-bisnor-5-cholene-3beta,22-diol
-
competitive inhibitor, 40% inhibition at 0.01 mM, 50% at 0.015 mM, resembles the intermediate 22-hydroxycholesterol but acts as an inhibitor rather than serving as a substrate
23-Amino-24-nor-5-cholen-3beta-ol
-
23-amine derivative, same steroid ring structure as cholesterol, competitive inhibitor with respect to cholesterol, 50% inhibition at 0.0001 mM, reversible cooperative binding
24-Amino-5-cholen-3beta-ol
-
24-amine derivative, amine attached in greater distance from steroid ring, same steroid ring structure as cholesterol, causes a progressive decrease in inhibitory potency, 50% inhibition at 0.0023 mM, reversible noncooperative binding
25-Amino-26,27-bisnor-5-cholesten-3beta-ol
-
25-amine derivative, amine attached in greater distance from steroid ring, causes a progressive decrease in inhibitory potency, 50% inhibition at more than 0.1 mM
adrenodoxin
-
oxidized form, high affinity to P-450scc, inhibits side chain cleavage by competition with reduced form
-
aminogluthetimide
-
-
Ca2+
-
inhibits side chain cleavage activity optimally activated by 100 mM NaCl
Ca2+
-
CaCl2 inhibits side chain cleavage activity at 100 mM NaCl, 50% inhibition with 0.07 mM in Tween 20 and 0.03 mM for vesicle-incorporated, Ca2+ does not affect binding of either cholesterol of oxidized adrenodoxin to P-450scc
cholesterol
-
inhibition above 0.003 mM, mitochondrial
Cholesterol sulfate
-
inhibition above 0.005 mM, mitochondrial
glycerol
-
substrate cholesterol, 50% inhibition at 25% glycerol, substrate 22(R)-hydroxycholesterol, 50% inhibition at 44% glycerol, substrate 20alpha-hydroxycholesterol, 50% inhibition at 48% glycerol, substrate 20alpha, 22(R)-dihydroxycholesterol, 50% inhibition at 51% glycerol
phosphatidyl choline
-
-
phosphatidyl ethanolamine
-
-
methoxychlor
-
pesticide of DDT, suicide inhibitor, competitive to cholesterol, substantial irreversible loss of activity, 5% inhibition within 5 min at 0.2 mM, decrease is suppressed by the presence of cholesterol
additional information
-
cholesterol analogues have shortened side chain and primary amine group, tested in presence of 0.07 mM cholesterol; steroid ring is suggested to bind to the substrate site on the enzyme and the amine is coordinated to the heme iron
-
additional information
-
amine binding to heme is important for tight inhibitor potency rather than the 5-androstene ring, 23,24-bisnor-5-cholen-3beta-ol-22-carboxamide is ineffective as inhibitor, side chain carbons 23-27 may play some role in positioning the substrate for hydroxylation; cholesterol analogues have shortened side chain and primary amine group, tested in presence of 0.07 mM cholesterol
-
additional information
-
no substrate inhibition with cytosolic enzyme, inhibitor of cholesterol-side-chain cleavage isolated from the cytosol of bovine adrenal cortex
-
additional information
-
mechanism-based inhibition, no inhibition with (20R)-22-thiacholesterol at 0.001 mM, inhibition by occupying the cholesterol binding pocket
-
additional information
-
inhibitors bind to substrate-heme complex, longer chain compounds possess inhibitory activity, phenyl ethyl compounds not
-
additional information
-
inactivation different in absence and presence of cholesterol, protective effect of cholesterol as well as 20alpha-hydroxycholesterol and deoxycorticosterone against inactivation by methoxychlor
-
additional information
-
leptin interferes with adrenocorticotropin/cAMP signaling, possibly through a janus kinase 2-phosphatidylinositol 3-kinase/akt-phosphodiesterase 3-cAMP pathway, to down-regulate the enzyme in NCI-H295 cells, leptin negatively controls ACTH/cholera toxin-induced CYP11A1 promoter activity to inhibit P450scc expression, mechanism, overview
-
additional information
-
S-nitroso-N-acetylpenicillamine inhibits enzyme transcription and translation in luteal cells
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,2-di-(2'-hexyl-decanoyl)-sn-glycero-3-phosphocholine
-
alpha-branched phosphatidylcholine, inclusion in vesicle-reconstituted system, partially in connection with the nonactivator lipids dimyristoyl-/dioleoyl-phosphatidylcholine, efficiency close to cardiolipin
-
1,2-di-(2'-octyl-dodecanoyl)-sn-glycero-phosphocholine
-
alpha-branched phosphatidylcholine, inclusion in vesicle-reconstituted system, partially in connection with the nonactivator lipids dimyristoyl-/dioleoyl-phosphatidylcholine, efficiency close to cardiolipin
-
Brij
-
56, 76 and 96
-
cardiolipin
-
affinity of P-450scc for cholesterol is increased
cardiolipin
-
most potent and effective activator lipid, binds to enzyme and enhances the binding of cholesterol
Emulgen
-
911 and 913
-
fatty acid
-
C18, natural detergents in DMPC vesicles, stimulation similar to octyl glucoside
glycerol
-
5-20% concentration, 20-50% increase of enzyme activity
octyl glucoside
-
high concentrations of this detergent cause 50% stimulation of cholesterol side-chain-cleavage in large unilamellar vesicles at low cholesterol concentration, 0.01 mM increase the proportion of P-450 bound by cholesterol
Phospholipid
-
cholesterol gains access to the cytochrome within micelles
Phospholipid
-
inclusion of P-450 into vesicles
Phospholipid
-
P-450scc reconstituted in vesicles, cholate-solubilized for small unilamellar dioleoylphosphatidylcholine vesicles, non-ionic detergent n-octyl glucoside used for large ones
Runx2
-
activation of CYP11A1 by the osteogenic transcription factor Runx2 may contribute to attenuation of osteoblast growth. Runx2 binds to the CYP11A1 gene promoter, CYP11A1 is a direct target of Runx2
-
Runx2
-
activation of CYP11A1 by the osteogenic transcription factor Runx2 may contribute to attenuation of osteoblast growth. Runx2 binds to the CYP11A1 gene promoter, CYP11A1 is a direct target of Runx2. Runx2 is rate limiting for CYP11A1 gene expression during differentation along the osteoblastic lineage
-
Triton X-100
-
effect onto P-450 itself suggested
Tween 20
-
small stabilizing and binding activating effect on ternary complex of adrenodoxin-cholesterol-P-450scc
Tween 20
-
-
Lipid
-
from adrenal mitochondria accelerates activity
additional information
-
activator of cholesterol side-chain cleavage isolated from the cytosol of bovine adrenal cortex
-
additional information
-
enzymatic activity is greatest at low ionic strength with a number of different ions
-
additional information
-
head and fatty acid groups have large effects on stimulation of activity, head group appears as major determinant of the lipid interaction with the P-450scc, 1-2 and 3-4 molecules of cardiolipin and the branched phosphatidylcholines, respectively, bind highly specific to P-450scc at an effector site distant from cholesterol binding site with a resultant stabilization of an optimal cholesterol-binding conformation of P-450scc
-
additional information
-
4-nonylphenol induces enzyme expression by 150%, overview
-
additional information
-
enzyme induction by gonadotropic stimuli, e.g. artificially by a salmon piuitary homogenate, in ovary
-
additional information
-
luteinizing hormone, progesterone, and prostaglandin E2 induce enzyme expression in luteal cells
-
additional information
-
P450scc induction by available nutrients and phytoplankton blooms
-
additional information
-
vitamin D3 and cholesterol are metabolized with comparable efficiencies in cyclodextrin, but the Km for both show a strong dependence on the cyclodextrin concentration, decreasing with decreasing cyclodextrin
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0181
-
17,20-dihydroxyvitamin D2
-
in 0.45% cyclodextrin
0.012
-
20-hydroxyvitamin D2
-
in 0.45% cyclodextrin
0.067
-
20-hydroxyvitamin D3
-
in the presence of 0.45% cyclodextrin
0.012
-
20alpha-hydroxycholesterol
-
-
0.0004
-
adrenodoxin
-
free
-
0.00056
-
adrenodoxin
-
+/-0.00004, complex between adrenodoxin and adrenodoxin reductase
-
0.0012
-
adrenodoxin
-
-
-
0.0005
-
cholesterol
-
mitochondrial
0.002
-
cholesterol
-
low concentration, both vesicle types
0.0091
-
cholesterol
-
in 0.45% cyclodextrin
0.0091
-
cholesterol
-
in the presence of 0.45% cyclodextrin
0.0165
-
cholesterol
-
cytosolic
0.164
-
cholesterol
-
-
0.19
-
cholesterol
-
-
0.3
-
cholesterol
-
large unilamellar vesicles, second type of reaction
0.39
-
cholesterol
-
-
1.18
-
cholesterol
-
in the presence of 4.5% cyclodextrin
0.0003
-
Cholesterol sulfate
-
mitochondrial
0.0175
-
vitamin D2
-
in 0.45% cyclodextrin
0.0296
-
vitamin D3
-
in the presence of 0.45% cyclodextrin
3.67
-
vitamin D3
-
in the presence of 4.5% cyclodextrin
0.0232
-
Cholesterol sulfate
-
cytosolic
additional information
-
additional information
-
decrease in concentration of adrenodoxin reductase causes a decrease in Km-values for cholesterol and adrenodoxin, in mitochondria, cholesterol is near-saturating for enzyme activity due to low and rate-limiting concentration of adrenodoxin reductase present
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.123
-
20-hydroxyvitamin D3
-
in the presence of 0.45% cyclodextrin
0.05
-
cholesterol
-
-
0.1
-
cholesterol
-
in the presence of 0.45% cyclodextrin
0.248
-
cholesterol
-
in the presence of 4.5% cyclodextrin
0.328
-
vitamin D3
-
in the presence of 0.45% cyclodextrin
1.6
-
vitamin D3
-
in the presence of 4.5% cyclodextrin
0.417
0.5
cholesterol
-
by large unilamellar vesicles
additional information
-
additional information
-
for small unilamellar vesicles 5fold lower
-
additional information
-
additional information
-
in 0.45% cyclodextrin, the kcat of cholesterol is 6.1 mol/min/mol P450scc, the kcat of vitamin D2 is 2.28 mol/min/mol P450scc, the kcat of 20-hydroxyvitamin D2 is 2.47 mol/min/mol P450scc and the kcat of 17,20-dihydroxyvitamin D2 is 0.33 mol/min/mol P450scc. In phosphatidylcholine vesicles, the kcat of cholesterol is 46 mol/min/mol P450scc, the kcat of vitamin D2 is 5.62 mol/min/mol P450scc, the kcat of 20-hydroxyvitamin D2 is 1.99 mol/min/mol P450scc and the kcat of 17,20-dihydroxyvitamin D2 is 0.21 mol/min/mol P450scc
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.83
-
20-hydroxyvitamin D3
-
in the presence of 0.45% cyclodextrin
293052
0.212
-
cholesterol
-
in the presence of 4.5% cyclodextrin
8550
11.17
-
cholesterol
-
in the presence of 0.45% cyclodextrin
8550
0.435
-
vitamin D3
-
in the presence of 4.5% cyclodextrin
17870
11.1
-
vitamin D3
-
in the presence of 0.45% cyclodextrin
17870
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
-
-
for cholesterol and 20alpha-hydroxycholesterol, 75 mM potassium phosphate buffer
7
-
-
assay at
7
-
-
assay at; reduction of P-450scc-cholesterol complex by reduced adrenodoxin
7.2
-
-
assay at
7.2
-
-
maximal adrenodoxin-induced absorbance with 0.03 mM cholesterol
7.3
-
-
assay at
7.4
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
7.5
-
less than 50% of maximal activity below and above range
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
-
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
15
42
-
tested in different dimyristoyl-phosphatidylcholine vesicles, breaks in activity at 27-30C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
enzyme expression pattern
Manually annotated by BRENDA team
-
epithelial ovarian carcinoma
Manually annotated by BRENDA team
-
primary, from corpora lutea at day 6 to 10 of the estrous cycle, semi-quatitative enzyme expression analysis
Manually annotated by BRENDA team
-
specific expressionin luteal cells, no expression in endothelial cells lining the blood vessels
Manually annotated by BRENDA team
-
basophilic cells, exclusively
Manually annotated by BRENDA team
-
the gonads of all fish first differentiate into ovaries first, and the oocytes gradually develope and increase in number as the ovaries grow. Then some cysts of differentiated spermatogenic germ cells appear in the ovaries and ambisexual gonads with both ovarian and testicular tissues formed, expression of cytochrome P450 cholesterol side-chain cleavage enzyme occurs in undifferentiated gonads, during gonadal sex differentiation, and in ovarian tissue more frequently than in testicular tissue, overview
Manually annotated by BRENDA team
-
female and male, expression pattern of P450scc mRNA during gonadal development using in situ hybridization, overview. In male gonads, expression of P450scc occurs in the interstitial somatic cells 15 days after hatching following the formation of the seminiferous tubule precursor, and is maintained in the interstitial somatic cells throughout testicular development. In the female gonad, expression of P450scc initially occurs in interstitial somatic cells 5 days after hatching and subsequently occurs continuously in the interstitial somatic cells of the developing ovary
Manually annotated by BRENDA team
-
pre-ovulatory follicle F1
Manually annotated by BRENDA team
-
renal cortex and medulla, distal convoluted tubule, and thick ascending limb of Henle's loop. The enzyme expression is higher in medulla than in cortex
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
renal cortex and medulla, distal convoluted tubule, and thick ascending limb of Henle's loop. The enzyme expression is higher in medulla than in cortex
-
Manually annotated by BRENDA team
-
adrenocortical cell line
Manually annotated by BRENDA team
-
dorsal root ganglion, spinal cord, dorsal horn, nociceptive supraspinal nuclei and somatosensory cortex
Manually annotated by BRENDA team
-
follicular cell, oocyte membrane
Manually annotated by BRENDA team
-
expresses an approximately 32-kDa truncated isoform of CYP11A1, expression of an approximately 32-kDa truncated isoform of CYP11A1
Manually annotated by BRENDA team
-
changes in localization in ovary during gonadal development, localization in the outer layer of the ovarian follicle and the thecal cell layer, the ovarian wall, and in ovigerous lamella epithelium, in late vitellogenic and migratory nucleus stages the enzyme is also localized in the granulosa cell layer, situ hybridization, overview
Manually annotated by BRENDA team
-
enzyme expression increases throughout the ovarian development
Manually annotated by BRENDA team
-
high levels in mature tissue
Manually annotated by BRENDA team
-
strong 450scc mRNA signal in the vitellogenic ovarian follicles of adult ovaries, P450scc is not detected in postvitellogenic follicles
Manually annotated by BRENDA team
-
expresses the full length 55-kDa isoform of CYP11A1
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
enzyme not entirely distributed in each interstitial cell, strong immunohistochemical reaction in cytoplasm of spermatogonia and some Sertoli cells
Manually annotated by BRENDA team
-
changes in localization in testis during gonadal development, localization in immature and type A spermatogonia, and after some days of development in all type B cells, and in Lydig cells and spermatocysts, in situ hybridization, overview
Manually annotated by BRENDA team
-
high level, expresses the full length 55-kDa isoform of CYP11A1
Manually annotated by BRENDA team
-
developing, in interstitial region between testicular tubules, expression pattern of medaka P450scc during testicular development, overview
Manually annotated by BRENDA team
-
low level
Manually annotated by BRENDA team
-
breast cancer cell, expresses both the 55-kDa isoform and the 32-kDa truncated isoform of CYP11A1
Manually annotated by BRENDA team
additional information
-
the enzyme is expressed mainly in steroidogenic tissue
Manually annotated by BRENDA team
additional information
-
tissue-specific expression pattern, overview
Manually annotated by BRENDA team
additional information
-
immunohistochemic analysis of enzyme localization
Manually annotated by BRENDA team
additional information
-
immunolocalization analysis in mollusc tissue using a polyclonal antibody against rat cholesterol side-chain cleavage enzyme, no activity in gonad, gills and kidney, overview
Manually annotated by BRENDA team
additional information
-
immunohistochemic localization analysis, overview
Manually annotated by BRENDA team
additional information
-
expression of the 32-kDa truncated isoform of CYP11A1 in HOB-04T8 cells
Manually annotated by BRENDA team
additional information
-
very low level of endogenous CYP11A1 in MC3T3 cells and Runx2-null osteoprogenitor cells
Manually annotated by BRENDA team
additional information
-
Immunohistochemical localization analysis
Manually annotated by BRENDA team
additional information
Rattus norvegicus Wistar
-
Immunohistochemical localization analysis
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
both full length and truncated isoforms are predominantely localized in the cytoplasm
Manually annotated by BRENDA team
-
adrenodoxin reductase and adrenodoxin are peripheral proteins on matrix side of inner membrane, P-450scc is integral membrane protein
Manually annotated by BRENDA team
-
adrenodoxin reductase and adrenodoxin are peripheral proteins on matrix side of inner membrane, P-450scc is integral membrane protein; integral to membrane
Manually annotated by BRENDA team
-
electron carriers and P-450 liquid-bound within mitochondrion
Manually annotated by BRENDA team
-
inner membrane; matrix side
Manually annotated by BRENDA team
-
membrane topology, overview
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
truncated form is nonmitochondrial
Manually annotated by BRENDA team
-
truncated form
Manually annotated by BRENDA team
additional information
-
all of the addressing sequences, containing transmembrane domains, provide effective insertion of the hybrid proteins AAC-mCYP11A1, Bcs1p(1-83)-mCYP11A1, DLD(1-72)-mCYP11A1 and Su9(1-116)-mCYP11A1 into the mitochondrial inner membrane. preAd-mCYP11A1 hybrid molecules are translocated across the inner membrane and tightly associated with the membrane on its matrix side but not membrane inserted. The mechanism of Ad-mCYP11A1 hybrid topogenesis in Escherichia coli cells differs from that of the topogenesis of its precursor form in yeast mitochondria
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
32000
-
-
truncated form, Western blot analysis
55000
-
-
full-length form, Western blot analysis
97000
-
-
sedimentation equilibrium
100000
-
-
native-PAGE, incomplete enzyme or molecular environmental conditions not optimal
200000
-
-
sedimentation equilibrium analysis
200000
-
-
native-PAGE, lowest single unit with high enzymatic activity
200000
-
-
sedimentation equilibrium performed in 100 mM potassium phosphate buffer, pH 7.6
220000
-
-
corpus luteum
225000
-
-
sedimentation equilibrium
400000
-
-
native-PAGE
415000
-
-
sedimentation equilibrium
470000
-
-
sedimentation equilibrium performed in 100 mM potassium phosphate buffer, pH 7.6
800000
-
-
exclusion chromatography
850000
-
-
sedimentation equilibrium analysis
850000
-
-
adrenal mitochondria
850000
-
-
-
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 60000, SDS-PAGE, molecular weights of bovine P-450 reported: 1 * 46000 and x * 53000
?
-
2,4,6,8 * 48000, SDS-PAGE, corpus luteum. x * 46000, x * 60000, x * 53000, x * 52000-53000 adrenal mitochondria
?
-
single band, SDS-PAGE
?
-
x * 120000, fusion protein of enzyme plus adrenodoxin reductase plus adrenodoxin
?
-
x * 59000, recombinant His-tagged enzyme, SDS-PAGE
?
-
x * 51400, SDS-PAGE
?
-
x * 52000, SDS-PAGE
tetramer
-
4 * 46000, sedimentation equilibrium analysis after guanidine treatment and SDS-PAGE
hexadecamer
-
16 * 53000, sedimentation equilibrium performed in 6 M guanidine after heating, 16 * 52000, SDS-PAGE. Can also exist in forms of 4 and 8 subunits after treatment with 100 mM potassium phosphate buffer, 7.6, with molecular weights of 200000 and 470000, respectively
additional information
-
the enzyme structure possesses a substrate access channel, the F-G loop is a membrane-interacting area
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
CYP11A1 in complex with (22R)-22-hydroxycholesterol, sitting drop vapour diffusion methdo, mixing of 0.001 ml of 23 mg/ml protein in 50 mM potassium phosphate, pH 7.2, 20% glycerol, 0.1 M NaCl, 0.1% octyl pentaethylene glycol ether, 1 mM EDTA, and 0.05 mM (22R)-22-hydroxycholesterol, with 0.001 ml of precipitant solution containing 14% PEG 1000, 20% glycerol, 12% JEFFAMINE ED-2001, 0.1 M MES, pH 7.0, and 10% isopropyl alcohol, 18C, overnight, X-ray diffraction structure determination and analysis at 2.8 A resolution, molecular replacement using rat mitochondrial CYP24A1
P00189
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
increase of complex formation of adrenodoxin and cytochrome P-450scc in absence of cholesterol with decrease of temperature to 6C, elevated temperature decreases the affinity of P-450scc for cholesterol
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
catalase, protects P-450scc against activity loss
-
glycerol, 50%, stabilizes
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Glycerol
-
induces sigmoidal low-spin response of otherwise high-spin spectrum, weakens adrenodoxin binding, inhibitory effect being substrate dependent
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 10 mM sodium phosphate buffer, pH 7.4, 0.1 mM EDTA, 20% glycerol, stable for months
-
-20C, 50 mM potassium phosphate buffer, pH 7.0, 50% glycerol, 3 months
-
-20C, 50% glycerol, for months
-
-20C, mitochondrial precipitate, 10 mM sodium phosphate buffer, pH 7.4, 0.1 mM EDTA
-
-20C, purified, 10 mM sodium phosphate buffer, pH 7.4, 0.1 mM EDTA, 20% glycerol, for months without loss of P-450 activity
-
-70C, mitochondrial pellet, 30-40 mg/ml, 100 mM potassium phosphate, pH 7.3, 0.2 mM EDTA
-
-80C, 50 mM potassium phosphate buffer, pH 7.0, 0.1 mM EDTA, 0.1 mM dithiothreitol, 0.01% cholate, a few days without substantial loss of activity
-
0C on ice, purified, 20 mM potassium phosphate buffer, pH 7.4, 20% glycerol, v/v, 0.1 mM EDTA, 0.1 mM dithioerythritol, 0.01% Emulgen 911, 3 weeks, without substantial loss of activity
-
4C, purified, 50 mM potassium phosphate, pH 7.3, 0.1 mM dithiothreitol, 10% glycerol, stable a few weeks
-
5C, 50 mM potassium phosphate buffer, pH 7.0, without glycerol, 21-43% decrease of activity within 30 days, completely lost in 4 months
-
purified, 25 mM potassium phosphate, pH 7.3, 0.05 mM EDTA, 0.05 mM dithiothreitol, 0.025 mM deoxycorticosterone, 0.25% Tween 20, 0.25% sodium cholate
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged CYP11A1 protein from Escherichia coli by nickel affinity chromatography
Q4KYY5
affinity chromatography
-
ammonium sulfate fractioning, aniline-Sepharose, adrenodoxin-Separose
-
ammonium sulfate precipitation, affinity chromatography
-
ammonium sulfate precipitation, affinity chromatography; DEAE-cellulose, adrenodoxin-Sepharose
-
cholate extraction, pyrophosphate treatment, affinity chromatography
-
cholic acid extraction, ammonium sulfate precipitation, DEAE-cellulose, hydroxylapatite and gel filtration
-
column chromatography, gel filtration
-
DEAE-cellulose, adrenodoxin-Sepharose
-
iso-octane and ammonium sulfate fractionating, gel filtration
-
precipitation with polyethylene glycol, affinity chromatography
-
recombinant C-terminally His4-tagged CYP11A1 by anion exchange, nickel affinity, hydroxylapatite, adrenodoxin affinity chromatography, and gel filtration
P00189
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
several ion exchange and heptyl-Sepharose hydrophobic chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
native enzyme partially by purification of mitochondrial inner membranes
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene CYP11A1, DNA and amino acid sequence determination and analysis, expression pattern analysis, functional expression in COS-7 cells
-
gene CYP11A1, expression as His-tagged protein in Escherichia coli
-
expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
heterologous expression in Escherichia coli
-
mutants and wild-type expressed in Escherichia coli
-
Nicotiana tabacum plants expressing CYP11A1 cDNA
-
recombinant expression of C-terminally His4-tagged CYP11A1
P00189
expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic analysis, and expression in COS-1 cells with adrenodoxin resulting in significantly more pregnenolone, co-expression with the steroidogenic acute regulatory protein and a human P450scc/adrenodoxin reductase/adrenodoxin fusion constructs. COS-1 cells transfected with a modified construct in which human P450scc is replaced by Dasyatis sabina P450scc show higher rates than cells transfected with Dasyatis sabina P450scc alone. Suncloning in Escherichia coli strain DH5alpha
D0EFX3, -
expressed from pCMV-SPORT6 vector
-
gene CYP11A1, DNA and amino acid sequence determination of wild-type and mutant enzymes, expression in HeLa cells and COS-1 cells, functional studies of P450scc RNA splicing
P05108
both full-length and an N-terminally truncated form amplified and inserted into TOPO TA PCR cloning vector and subsequently subcloned into the EcoRI restriction site of pCMV-tag2B vector to obtain CYP11A1 proteins with an N-terminal Flag tag or into pEGFP-C2 vector to yield an N-terminal GFP tag
-
gene p450scc, semi-/quantitative RT-PCR expression analysis, overview
-
DNA and amino acid sequence determination and analysis, expression analysis and sequence comparisons
-
DNA sequence determination, quantitative enzyme expression analysis in brain prior and after treatment with 4-nonylphenol
-
expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
hybrid proteins AAC-mCYP11A1, Bcs1p(183)-mCYP11A1, Su9(1-116)-mCYP11A1, preAd-mCYP11A1, DLD(1-72)-mCYP11A1 and COXIV-mCYP11A1 expressed in Saccharomyces cerevisiae strain 2805. Escherichia coli strain JM109 transformed with the plasmid pTrc99(A)/Ad-mCYP11A1
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
mRNA levels for CYP11A1 are significantly lower in subordinate follicles in comparison to dominant follicles and this effect is maintained following adjustment for follicle size
-
contents of soluble protein and carbohydrates in leaves and seeds of transgenic Nicotiana tabacum plants are essentially higher than the contents of these components in leaves and seeds of control plants
-
CYP11A1 is elevated in dominant follicles. CYP11A1 mRNA levels are highly correlated with the focimatrix genes COL4A1, NID1 and -2 and HSPG2. Focimatrix may potentially regulate CYP11A1 expression, and the regulation of both may be important in follicular dominance
-
14 days exposure of previtellogenic ovarian oocytes to nonylphenol produces a unique and consistent concentration-specific pattern of modulation of StAR and P450scc gene expression, increasing from 0 (control) to 1 and 10 micromol, and decreasing at 50 and 100 micromol
-
testosterone significantly increases P450scc in F1 granulosa cells after 3 h at 10 and 100 ng/ml
-
CYP11A1 expression is induced by Runx2in osteoblasts
-
P450scc expression is reduced in Leydig cells treated with synthetic hormone diethylstilbestrol and natural hormone 17beta-estradiol. Diethylstilbestrol causes histone deacetylation in the P450scc promoter region, while 17beta-estradiol does not
-
CYP11A1 mRNA expression is dramatically induced within 2 h after introduction of Runx2 protein into Runx2-null cells. CYP11A1 gene expression is induced during osteoblastic differentiation
-
induction of P450scc mRNA expression by 8-Br-cAMP
-
expression of StAR and P450scc transcripts in non-steroidogenic tissues
-
relationship between cortisol production and induction of transcription of steroidogenic acute regulatory (StAR) protein and P450scc. Exposure of juveniles to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and the synthetic estrogen 17alpha-ethynylestradiol produces transcriptional modulations of StAR and P450scc expression in interrenal tissue. In juvenile salmon exposed to 17alpha-ethynylestradiol, expression of P450scc mRNA is detectable in the trunk kidney, while StAR mRNA is not quantifiable. 17alpha-ethynylestradiol produces time- and concentration-specific effects on the expression of the StAR, P450scc, P450arom isoforms and IGF-2 genes in gonadal tissues. In liver and kidney tissues exposed to the endocrine disrupting chemical 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, significant induction of both StAR and P450scc mRNA
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K103Q
-
decrease of stability
K103Q
-
expression similar to wild-type, decreased stability or an altered heme or substrate pocket, B'-C loop, no change in interaction of P-450scc and adrenodoxin
K104Q
-
dramatic decrease in expression level
K104Q
-
decreased expression, B'-C loop, no change in interaction of P-450scc and adrenodoxin
K109Q
-
dramatic changes in folding and heme insertion
K109Q
-
change in folding, thus, an inability of heme to be retained, helix C, no change in interaction of P-450scc and adrenodoxin
K110Q
-
folding and heme insertion not affected
K110Q
-
expression similar to wild-type, helix C, does not appear to play a role in adrenodoxin binding because it shows no change in interaction of P-450scc and adrenodoxin
K145Q
-
-
K145Q
-
expression similar to wild-type, helix D
K148Q
-
expression level is not affected, extreme instable and rapid denaturation
K148Q
-
extremely unstable, helix D
K267Q
-
participation in electrostatic interaction of P-450scc with adrenodoxin
K338Q
-
removed from heme group but still very important for interaction with adrenodoxin, K helix
K342Q
-
removed from heme group but still very important for interaction with adrenodoxin, K helix
K394Q
-
functional parameters decreased because substitution is close to 405 position, but to much lower extend
K394Q
-
expression similar to wild-type, 'meander', involved in the interaction of P-450scc with its electron-transfer partners
K403Q
-
functional parameters decreased because substitution is close to 405 position, but to much lower extend, shows importance of this residue for electrostatic interaction with negatively charged residues of ferredoxin
K403Q
-
participation in electrostatic interaction of P-450scc with adrenodoxin
K403Q
-
expression similar to wild-type, located between the meander and the heme-binding region, important role in electrostatic interactions with adrenodoxin, ability to bind adrenodoxin affected to lower extent than K405Q
K405Q
-
dramatic loss of activity, shows importance of this residue for electrostatic interaction with negatively charged residues of ferredoxin
K405Q
-
participation in electrostatic interaction of P-450scc with adrenodoxin
R425Q
-
most harmful substitution, L helix, heme-binding region
R425Q/R426C
-
double mutant, most harmful substitution
R425Q/R426Q
-
double mutant, most harmful substitution
R426Q
-
participation in electrostatic interaction of P-450scc with adrenodoxin
R426Q
-
expression similar to wild-type, serious changes in proteine folding and ability to insert and bind heme correctly, unable to catalyze cholesterol side chain cleavage reaction, although it is able to bind cholesterol, L helix, heme-binding region, important role in electrostatic interactions with adrenodoxin
c835delA
P05108
a naturally occuring CYP11A1 frameshift mutation, heterozygous mutant, phenotype, overview
V415E
P05108
a naturally occuring CYP11A1 missense mutation, heterozygous mutant, phenotype, overview
K405Q
-
expression similar to wild-type, 4fold decrease in efficiency of enzymatic reduction by adrenodoxin and adrenodoxin reductase, and a 3.3fold decrease of cholesterol side chain cleavage activity, located between the meander and the heme-binding region, important role in electrostatic interactions with adrenodoxin
additional information
-
site-directed mutagenesis, no evident changes in functional properties for KQ mutants, 103, 110, 145, 394 and 403 with activities between 69 and 86% of wild-type
additional information
-
site directed mutagenesis. complex stabilizing salt bridges: K403 of P-450scc with D76 of adrenodoxin, K405 with D72, R426 with E73 and K267 with E47, multiple electrostatic interactions between the negatively charged residues of adrenodoxin and positively charged groups of P-450scc
additional information
-
construction of fusion proteins of enzyme plus adrenodoxin plus adrenodoxin reductase, fusion in order enzyme - adrenodoxin - adrenodoxin reductase gives 30-fold higher enzymatic activity than fusion in same order with human enzyme and 14-fold higher activity than fusion with human enzyme in order adrenodoxin reductase adrenodoxin enzyme. CO-difference spectra do not show the presence of a normally folded enzyme moiety
L141W
P05108
a naturally occuring CYP11A1 missense mutation, heterozygous mutant, phenotype, overview
additional information
-
construction of fusion proteins of enzyme plus adrenodoxin plus adrenodoxin reductase, fusion in order bovine enzyme - adrenodoxin - adrenodoxin reductase gives 30-fold higher enzymatic activity than fusion in same order with human enzyme and 14-fold higher activity than fusion with human enzyme in order adrenodoxin reductase adrenodoxin enzyme. Dimers of enzyme with adrenodoxin in order enzyme adrenodoxin or adrenodoxin enzyme show minimal side chain cleavage activity. CO difference spectra reveal a denatured cytochrome P450 in dimer fusion proteins
additional information
-
mutation of a cysteine residue in the F-G loop leads to altered membrane interaction and activity
additional information
P05108
mutation of CYP11A1 leads to individuals with 46,XY disorders of sex development and primary adrenal failure, identification of P450scc mutations in children, analysis of genotype/phenotype correlations, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
-
the vitamin D3 derivatives produced by the action of P450scc are good candidates for use in the therapy of hyperproliferative disorders
medicine
-
treatment of certain hormone-related pathologies
medicine
-
significant inversed statistical correlation of enzyme immunoreactivity with residual size of tumor in epithelial ovarian carcinoma, but correlation is not an independent prognostic value
biotechnology
-
the development of a cholesterol biosensor based on screen-printed electrodes modified with multi-walled carbon nanotubes and with the cytochromes P450scc may ensure a high sensitivity. Role of the nanotubes in mediating electron transfer to the cytochrome P450scc is verified as further improved with respect to the case of rhodium-graphite electrodes modified by the use of gold nanoparticles