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Literature summary for 1.14.14.25 extracted from

  • Mast, N.; White, M.A.; Bjorkhem, I.; Johnson, E.F.; Stout, C.D.; Pikuleva, I.A.
    Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain (2008), Proc. Natl. Acad. Sci. USA, 105, 9546-9551.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
cholesterol 3-sulfate i.e. CH-35 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
His-tagged enzyme Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
a recombinant C-terminally His4-tagged CYP46A1 lacking the first 50 N-terminal amino acid residues, substrate-free enzyme or enzyme in complex with cholesterol 3-sulfate, X-ray diffraction structure determination and analysis at 2.4 A and 1.9 A resolution, respectively, structure modeling Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information construction of an mutant CYP46A1, in which the first 50 N-terminal amino acid residues are deleted, and a His4 tag is added at the C-terminus. The truncation removed a 23-residue transmembrane-anchoring domain and renders this membrane P450 more soluble compared to the wild-type, overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
clobenpropit complete inhibition Homo sapiens
thioperamide 66% inhibition Homo sapiens
tranylcypromine complete inhibition Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0015
-
(24S)-24-hydroxycholesterol recombinant truncation mutant enzyme Homo sapiens
0.0033
-
cholesterol 3-sulfate recombinant truncation mutant enzyme Homo sapiens
0.0039
-
(24S)-24-hydroxycholesterol recombinant wild-type enzyme Homo sapiens
0.0049
-
cholesterol 3-sulfate recombinant wild-type enzyme Homo sapiens
0.0054
-
cholesterol recombinant wild-type enzyme Homo sapiens
0.0077
-
cholesterol recombinant truncation mutant enzyme Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ a heme-containing cytochrome P450 enzyme Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2 Homo sapiens
-
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y6A2
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme by nickel affinity chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
-
Homo sapiens (24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
r
cholesterol 3-sulfate + [reduced NADPH-hemoprotein reductase] + H+ + O2
-
Homo sapiens (24S)-24-hydroxycholesterol 3-sulfate + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
additional information active site structure and substrate binding, overview Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
CYP46A1
-
Homo sapiens
cytochrome P450 46A1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0018
-
cholesterol recombinant wild-type enzyme Homo sapiens
0.0072
-
cholesterol recombinant truncation mutant enzyme Homo sapiens
0.0076
-
cholesterol 3-sulfate recombinant wild-type enzyme Homo sapiens
0.0142
-
(24S)-24-hydroxycholesterol recombinant truncation mutant enzyme Homo sapiens
0.0153
-
(24S)-24-hydroxycholesterol recombinant wild-type enzyme Homo sapiens
0.042
-
cholesterol 3-sulfate recombinant truncation mutant enzyme Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.2
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
cytochrome P450
-
Homo sapiens
heme
-
Homo sapiens
NADPH
-
Homo sapiens