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Literature summary for 1.14.14.19 extracted from

  • Auchus, R.J.; Miller, W.L.
    Molecular modeling of human P450c17 (17alpha-hydroxylase/17,20-lyase): insights into reaction mechanisms and effects of mutations (1999), Mol. Endocrinol., 13, 1169-1182.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
cytochrome b5 acts as allosteric facilitator but not as electron donor, increases 17,20-lyase activity Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression in Saccharomyces cerevisiae strain W303B of the K89N-mutant Homo sapiens

Protein Variants

Protein Variants Comment Organism
K89N 78% loss of 17,20-lyase activity and 20% loss of 17alpha-hydroxylase activity Homo sapiens
R347H loss of 17,20-lyase activity to a greater extent than 17alpha-hydroxylase activity Homo sapiens
R358Q loss of 17,20-lyase activity to a greater extent than 17alpha-hydroxylase activity Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
17-hydroxypregnenolone competitive inhibitor of 17alpha-hydrolase activity Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0004
-
17-hydroxypregnenolone wild type enzyme Homo sapiens
0.0008
-
17-hydroxypregnenolone K89N mutant expressed in Saccharomyces cerevisiae Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Fe3+ heme Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens it catalyzes steroid 17alpha-hydroxylase and 17,20-lyase activities in the biosynthesis of androgens, estrogens and cortisol ?
-
?
pregnenolone + AH2 + O2 Homo sapiens
-
17alpha-hydroxypregnenolone + A + H2O product eliminates at C20,21 acetate to yield dehydroepiandrosterone ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P05093
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information both the lyase and hydroxylase activities proceed from a common steroid-binding geometry by an iron oxene mechanism Homo sapiens ?
-
?
additional information it catalyzes steroid 17alpha-hydroxylase and 17,20-lyase activities in the biosynthesis of androgens, estrogens and cortisol Homo sapiens ?
-
?
pregnenolone + AH2 + O2
-
Homo sapiens 17alpha-hydroxypregnenolone + A + H2O product eliminates at C20,21 acetate to yield dehydroepiandrosterone ?

Synonyms

Synonyms Comment Organism
P450c17
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0003
-
17-hydroxypregnenolone R347H-mutant, inhibiton of 17alpha-hydrolase activity Homo sapiens
0.0005
-
17-hydroxypregnenolone K89N-mutant, inhibiton of 17alpha-hydrolase activity Homo sapiens
0.0007
-
17-hydroxypregnenolone wild type, inhibiton of 17alpha-hydrolase activity Homo sapiens
0.0008
-
17-hydroxypregnenolone R358Q-mutant, inhibiton of 17alpha-hydrolase activity Homo sapiens