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(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
overall reaction
-
-
?
(20S)-22-thiacholesterol + reduced adrenodoxin + O2
(20S,22R)-22-thiacholesterol S-oxide + (20S,22S)-22-thiacholesterol S-oxide
-
-
(22R)-sulfoxide preferentially formed by a factor of 4.2 to 1 over (22S)-sulfoxide
?
17,20-dihydroxyvitamin D2 + reduced adrenodoxin + O2
17,20,24-trihydroxyvitamin D2 + oxidized adrenodoxin + O2
-
is slowly metabolized
-
-
?
20,23-dihydroxyvitamin D3 + reduced adrenodoxin + O2
17,20,23-trihydroxyvitamin D3 + oxidized adrenodoxin + H2O
-
-
-
-
?
20,23-dihydroxyvitamin D3 + reduced adrenodoxin + O2
17alpha,20,23-trihydroxyvitamin D3 + oxidized adrenodoxin + H2O
-
-
-
-
?
20-hydroxyvitamin D2 + reduced adrenodoxin + O2
17,20,24-trihydroxyvitamin D2 + oxidized adrenodoxin + O2
-
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
-
-
-
-
?
20-hydroxyvitamin D3 + reduced adrenodoxin + O2
20,23-dihydroxyvitamin D3 + oxidized adrenodoxin + H2O
-
-
-
-
?
20alpha, 22(R)-dihydroxycholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
-
-
-
-
?
20alpha-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
22(R)-hydroxycholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
-
-
-
-
?
22(R)-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
? + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
cholesterol + reduced adrenodoxin + O2 + H+
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
-
r
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
cholesterol sulfate + reduced adrenodoxin + O2
pregnenolone sulfate + 17-hydroxy-pregnenolone + dehydroisoandrosterone sulfate + oxidized adrenodoxin + H2O
-
-
-
?
vitamin D2 + reduced adrenodoxin + O2
17,20,24-trihydroxyvitamin D2 + oxidized adrenodoxin + H2O
-
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
additional information
?
-
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
product binding structure analysis, detailed overview
-
-
?
20alpha-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
20alpha-hydroxycholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
isocapraldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
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
-
first step in biosynthesis of all steroid hormones
isocaproic aldehyde additional product
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
-
isocaproaldehyde produced besides
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
intermediates (22R)-22-hydroxycholesterol and (20R,22R)-20,22-dihydroxycholesterol from hydroxylation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
intermediates (22R)-22-hydroxycholesterol and (20R,22R)-20,22-dihydroxycholesterol from hydroxylation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
20- or 22-hydroxycholesterol and 20,22-dehydroxycholesterol are putative intermediates
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
regioselective and stereospecific transformation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
intermediates 22R-hydroxycholesterol and 20alpha,22R-dihydroxycholesterol from hydroxylation
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
without demonstrable accumulation of putative intermediates 20alpha-hydroxycholesterol and 20alpha,22-dehydroxycholesterol
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
stable intermediates: 22-hydroxycholesterol and 20,22-dihydroxycholesterol
-
?
cholesterol + reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenodoxin + H2O
-
hydroxylation of cholesterol at C-22, then C-20, followed by oxidative scission of the glycol to get pregnenolone
-
?
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
-
-
-
-
?
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
-
metabolic regulation of enzyme expression, overview
-
-
?
vitamin D3 + reduced adrenodoxin + O2
20-hydroxyvitamin D3 + oxidized adrenodoxin + H2O
-
-
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
-
is hydroxylated with lower efficiency than cholesterol
-
-
?
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
the enzyme is important in steroidogenesis, regulatory mechanism, overview
-
-
?
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(20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2
pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
-
-
-
?
(22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2
(20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + 2 reduced adrenodoxin + O2
(22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
overall reaction
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
cholesterol + reduced adrenal ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin
-
-
-
-
?
cholesterol + reduced ferredoxin + O2
pregnenolone + 4-methylpentanal + oxidized ferredoxin
-
metabolic regulation of enzyme expression, overview
-
-
?
additional information
?
-
-
the enzyme is important in steroidogenesis, regulatory mechanism, overview
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
precursor of all steroid hormones
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
-
isocapraldehyde additional product
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
first step in biosynthesis of all steroid hormones
-
?
cholesterol + 6 reduced adrenodoxin + 3 O2
pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O
-
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
-
first step in biosynthesis of all steroid hormones
isocaproic aldehyde additional product
?
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(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-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
-
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
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
phosphatidyl ethanolamine
-
-
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
-
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
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
additional information
-
cholesterol analogues have shortened side chain and primary amine group, tested in presence of 0.07 mM cholesterol
-
additional information
-
cholesterol analogues have shortened side chain and primary amine group, tested in presence of 0.07 mM cholesterol
-
additional information
-
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
-
additional information
-
no substrate inhibition with cytosolic enzyme, inhibitor of cholesterol-side-chain cleavage isolated from the cytosol of bovine adrenal cortex
-
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
-
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
-
S-nitroso-N-acetylpenicillamine inhibits enzyme transcription and translation in luteal cells
-
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100000
-
native-PAGE, incomplete enzyme or molecular environmental conditions not optimal
120000
-
x * 120000, fusion protein of enzyme plus adrenodoxin reductase plus adrenodoxin
225000
-
sedimentation equilibrium
415000
-
sedimentation equilibrium
470000
-
sedimentation equilibrium performed in 100 mM potassium phosphate buffer, pH 7.6
48000
-
2,4,6,8 * 48000, SDS-PAGE, corpus luteum. x * 46000, x * 60000, x * 53000, x * 52000-53000 adrenal mitochondria
800000
-
exclusion chromatography
97000
-
sedimentation equilibrium
200000
-
sedimentation equilibrium analysis
200000
-
sedimentation equilibrium performed in 100 mM potassium phosphate buffer, pH 7.6
200000
-
native-PAGE, lowest single unit with high enzymatic activity
46000
-
x * 60000, SDS-PAGE, molecular weights of bovine P-450 reported: 1 * 46000 and x * 53000
46000
-
2,4,6,8 * 48000, SDS-PAGE, corpus luteum. x * 46000, x * 60000, x * 53000, x * 52000-53000 adrenal mitochondria
46000
-
4 * 46000, sedimentation equilibrium analysis after guanidine treatment and SDS-PAGE
52000
-
x * 52000, SDS-PAGE
52000
-
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
53000
-
x * 60000, SDS-PAGE, molecular weights of bovine P-450 reported: 1 * 46000 and x * 53000
53000
-
2,4,6,8 * 48000, SDS-PAGE, corpus luteum. x * 46000, x * 60000, x * 53000, x * 52000-53000 adrenal mitochondria
53000
-
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
60000
-
x * 60000, SDS-PAGE, molecular weights of bovine P-450 reported: 1 * 46000 and x * 53000
60000
-
2,4,6,8 * 48000, SDS-PAGE, corpus luteum. x * 46000, x * 60000, x * 53000, x * 52000-53000 adrenal mitochondria
850000
-
-
850000
-
sedimentation equilibrium analysis
850000
-
adrenal mitochondria
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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
R425Q
-
most harmful substitution, L helix, heme-binding region
R425Q/R426C
-
double mutant, most harmful substitution
R425Q/R426Q
-
double mutant, most harmful substitution
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
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
-
participation in electrostatic interaction of P-450scc with adrenodoxin
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
-
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
-
participation in electrostatic interaction of P-450scc with adrenodoxin
K405Q
-
dramatic loss of activity, shows importance of this residue for electrostatic interaction with negatively charged residues of ferredoxin
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
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
additional information
construction of a fusion protein consisting of cytochrome P450scc (CYP11A1), adrenodoxin and adrenodoxin reductase including 2A peptide from Picornaviridae which is capable of self-cleavage. Introduction to Escherichia coli leads to a high level of expression but no cleavage. In yeast Saccharomyces cerevisiae, the discrete proteins P450scc-2A, adrenodoxin-2A and adrenodoxin reductase are expressed, with a significant proportion present in a fusion adrenodoxin-2A-adrenodoxin reductase. The enzyme system is catalytically active
additional information
-
construction of a fusion protein consisting of cytochrome P450scc (CYP11A1), adrenodoxin and adrenodoxin reductase including 2A peptide from Picornaviridae which is capable of self-cleavage. Introduction to Escherichia coli leads to a high level of expression but no cleavage. In yeast Saccharomyces cerevisiae, the discrete proteins P450scc-2A, adrenodoxin-2A and adrenodoxin reductase are expressed, with a significant proportion present in a fusion adrenodoxin-2A-adrenodoxin reductase. The enzyme system is catalytically active
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
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Hanukoglu, I.; Jefcoate, C.R.
Mitochondrial cytochrome P-450sec. Mechanism of electron transport by adrenodoxin
J. Biol. Chem.
255
3057-3061
1980
Bos taurus
brenda
Hanukoglu, I.; Spitsberg, V.; Bumpus, J.A.; Dus, K.M.; Jefcoate, C.R.
Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover
J. Biol. Chem.
256
4321-4328
1981
Bos taurus
brenda
Hanukoglu, I.; Privalle, C.T.; Jefcoate, C.R.
Mechanisms of ionic activation of adrenal mitochondrial cytochromes P-450scc and P-45011beta
J. Biol. Chem.
256
4329-4335
1981
Bos taurus
brenda
Wang, H.P.; Kimura, T.
Purification and characterization of adrenal cortex mitochondrial cytochrome P-450 specific for cholesterol side chain cleavage activity
J. Biol. Chem.
251
6068-6074
1976
Bos taurus
brenda
Nakajin, S.; Ishii, Y.; Shinoda, M.
Binding of Triton X-100 to purified cytochrome P-450scc and enhancement of the cholesterol side chain cleavage activity
Biochem. Biophys. Res. Commun.
87
524-531
1979
Bos taurus
brenda
Hume, R.; Kelly, R.W.; Taylor, P.L.; Boyd, G.S.
The catalytic cycle of cytochrome P-450scc and intermediates in the conversion of cholesterol to pregnenolone
Eur. J. Biochem.
140
583-591
1984
Bos taurus
brenda
Shikita, M.; Hall, P.F.
Cytochrome P-450 from bovine adrenocortical mitochondria: an enzyme for the side chain cleavage of cholesterol. I. Purification and properties
J. Biol. Chem.
248
5598-5604
1973
Bos taurus
brenda
Takemori, S.; Sukara, K.; Hashimoto, K.; Hashimoto, M.; Sato, H.; Gomi, T.; Katagiri, M.
Purification of cytochrome P-450 from bovine adrenocortical mitochondria by an aniline-Sepharose and the properties
Biochem. Biophys. Res. Commun.
63
588-593
1975
Bos taurus
brenda
Dhariwal, M.S.; Jefcoate, C.R.
Cholesterol metabolism by purified cytochrome P-450scc is highly stimulated by octyl glucoside and stearic acid exclusively in large unilamellar phospholipid vesicles
Biochemistry
28
8397-8402
1989
Bos taurus
brenda
Lambeth, J.D.; Kriengsiri, S.
Cytochrome P-450scc-adrenodoxin interactions. Ionic effects on binding, and regulation of cytochrome reduction by bound steroid substrates
J. Biol. Chem.
260
8810-8816
1985
Bos taurus
brenda
Nagahisa, A.; Foo, T.; Gut, M.; Orme-Johnson, W.H.
Competitive inhibition of cytochrome P-450scc by (22R)- and (22S)-22-aminocholesterol. Side-chain stereochemical requirements for C-22 amine coordination to the active-site heme
J. Biol. Chem.
260
846-851
1985
Bos taurus
brenda
Kashiwagi, K.; Dafeldecker, W.P.; Salhanick, H.A.
Purification and characterization of mitochondrial cytochrome P-450 associated with cholesterol side chain cleavage from bovine corpus luteum
J. Biol. Chem.
255
2606-2611
1980
Bos taurus
brenda
Sheets, J.J.; Vickery, L.E.
Active site-directed inhibitors of cytochrome P-450scc. Structural and mechanistic implications of a side chain-substituted series of amino-steroids
J. Biol. Chem.
258
11446-11452
1983
Bos taurus
brenda
Sheets, J.J.; Vickery, L.E.
C-22-Substituted steroid derivatives as substrate analogues and inhibitors of cytochrome P-450scc
J. Biol. Chem.
258
1720-1725
1983
Bos taurus
brenda
Warne, P.A.; Greenfield, N.J.; Lieberman, S.
Modulation of the kinetics of cholesterol side-chain cleavage by an activator and by an inhibitor isolated from the cytosol of the cortex of bovine adrenals
Proc. Natl. Acad. Sci. USA
80
1877-1881
1983
Bos taurus
brenda
Shikita, M.; Hall, P.F.
Cytochrome P-450 from bovine adrenocortical mitochondria: an enzyme for the side chain cleavage of cholesterol. II. Subunit structure
J. Biol. Chem.
248
5605-5609
1973
Bos taurus
brenda
Miao, E.; Joardar, S.; Zuo, C.; Cloutier, N.J.; Nagahisa, A.; Byon, C.; Wilson, S.R.; Orme-Johnson, W.H.
Cytochrome P-450scc-mediated oxidation of (20S)-22-thiacholesterol: Characterization of mechanism-based inhibition
Biochemistry
34
8415-8421
1995
Bos taurus
brenda
Schwarz, D.; Kisselev, P.; Wessel, R.; Jueptner, O.; Schmid, R.D.
alpha-Branched 1,2-diacyl phosphatidylcholines as effectors of activity of cytochrome P450SCC (CYP11A1). Modeling the structure of the fatty acyl chain region of cardiolipin
J. Biol. Chem.
271
12840-12846
1996
Bos taurus
brenda
Lepesheva, G.I.; Azeva, T.N.; Strushkevich, N.V.; Gilep, A.A.; Usanov, S.A.
Site-directed mutagenesis of cytochrome P450scc (CYP11A1). Effect of lysine residue substitution on its structural and functional properties
Biochemistry (Moscow)
65
1409-1418
2000
Bos taurus
brenda
Ahmed, S.
The use of the novel substrate-heme complex approach in the derivation of a representation of the active site of the enzyme cholesterol side chain cleavage
Biochem. Biophys. Res. Commun.
274
821-824
2000
Bos taurus
brenda
Tsujita, M.; Ichikawa, Y.
Substrate-binding region of cytochrome P-450scc (P-450 XIA1). Identification and primary structure of the cholesterol binding region in cytochrome P-450scc
Biochim. Biophys. Acta
1161
124-130
1993
Bos taurus
brenda
Usanov, S.A.; Graham, S.E.; Lepesheva, G.I.; Azeva, T.N.; Strushkevich, N.V.; Gilep, A.A.; Estabrook, R.W.; Peterson, J.
Probing the interaction of bovine cytochrome P450scc (CYP11A1) with adrenodoxin: evaluating site-directed mutations by molecular modeling
Biochemistry
41
8310-8320
2002
Bos taurus
brenda
Headlam, M.J.; Tuckey, R.C.
The effect of glycerol on cytochrome P450scc (CYP11A1) spin state, activity, and hydration
Arch. Biochem. Biophys.
407
95-102
2002
Bos taurus
brenda
Nazarov, P.A.; Drutsa, V.L.; Miller, W.L.; Shkumatov, V.M.; Luzikov, V.N.; Novikova, L.A.
Formation and functioning of fused cholesterol side-chain cleavage enzymes
DNA Cell Biol.
22
243-252
2003
Bos taurus, Homo sapiens
brenda
Rekawiecki, R.; Nomik, M.; Kotwica, J.
Stimulatory effect of LH, PGE2 and progesterone on StAR protein, cytochrome P450 cholesterol side chain cleavage and 3beta hydroxysteroid dehydrogenase gene expression in bovine luteal cells
Prostaglandins other Lipid Mediat.
78
169-184
2005
Bos taurus
brenda
Chiu, C.H.; Wei, H.W.; Wu, L.S.
Generation and utilization of P450 cholesterol side-chain cleavage enzyme and 3beta-hydroxysteroid dehydrogenase antibodies for universal detection
J. Immunoassay Immunochem.
29
152-160
2008
Bos taurus, Sus scrofa, Capra aegagrus
brenda
Nguyen, M.N.; Slominski, A.; Li, W.; Ng, Y.R.; Tuckey, R.C.
Metabolism of vitamin d2 to 17,20,24-trihydroxyvitamin d2 by cytochrome p450scc (CYP11A1)
Drug Metab. Dispos.
37
761-767
2009
Bos taurus
brenda
Tuckey, R.C.; Li, W.; Zjawiony, J.K.; Zmijewski, M.A.; Nguyen, M.N.; Sweatman, T.; Miller, D.; Slominski, A.
Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc
FEBS J.
275
2585-2596
2008
Bos taurus
brenda
Spivak, S.; Berdichevets, I.; Iarmolinskiǐ, D.; Maneshina, T.; Shpakovskiǐ, G.; Kartel, N.
Construction and characteristics of transgenic tobacco Nicotiana tabacum L. plants expressing CYP11A1 cDNA encoding cytochrome P450scc
Genetika
45
1217-1224
2009
Bos taurus
brenda
Tuckey, R.C.; Nguyen, M.N.; Slominski, A.
Kinetics of vitamin D3 metabolism by cytochrome P450scc (CYP11A1) in phospholipid vesicles and cyclodextrin
Int. J. Biochem. Cell Biol.
40
2619-2626
2008
Bos taurus
brenda
Pikuleva, I.A.; Mast, N.; Liao, W.L.; Turko, I.V.
Studies of membrane topology of mitochondrial cholesterol hydroxylases CYPs 27A1 and 11A1
Lipids
43
1127-1132
2008
Bos taurus
brenda
Irving-Rodgers, H.F.; Harland, M.L.; Sullivan, T.R.; Rodgers, R.J.
Studies of granulosa cell maturation in dominant and subordinate bovine follicles: novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol side-chain cleavage CYP11A1
Reproduction
137
825-834
2009
Bos taurus
brenda
Mast, N.; Annalora, A.; Lodowski, D.; Palczewski, K.; Stout, C.; Pikuleva, I.
Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1
J. Biol. Chem.
286
5607-5613
2011
Bos taurus (P00189)
brenda
Kubeil, C.; Yeung, J.; Tuckey, R.; Rodgers, R.; Martin, L.
Membrane-mediated protein-protein interactions of cholesterol side-chain cleavage cytochrome P450 with its associated electron transport proteins
ChemPlusChem
81
995-1002
2016
Bos taurus (P00189)
-
brenda
Efimova, V.S.; Isaeva, L.V.; Makeeva, D.S.; Rubtsov, M.A.; Novikova, L.A.
Expression of cholesterol hydroxylase/lyase system proteins in yeast S. cerevisiae cells as a self-processing polyprotein
Mol. Biotechnol.
59
394-406
2017
Bos taurus (P00189), Bos taurus
brenda