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Literature summary for 1.14.14.19 extracted from

  • Estrada, D.F.; Laurence, J.S.; Scott, E.E.
    Substrate-modulated cytochrome P450 17A1 and cytochrome b5 interactions revealed by NMR (2013), J. Biol. Chem., 288, 17008-17018.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
cytochrome b5 recombinant human microsomal wild-type protein and mutants E48Q, E49Q, and V50S, enzyme interaction analysis by NMR, overview. Substrate-modulated interactions of cytochrome P450 17A1 and cytochrome b5, by reversible binding, involving enzyme anionic residues Glu48 or Glu49 and corresponding cationic CYP17A1 residues Arg347, Arg358, and Arg449. The CYP17A1/b5 interaction is stronger when the hydroxylase substrate pregnenolone is present in the CYP17A1 active site than when the lyase substrate 17alpha-hydroxypregnenolone is in the active site Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of wild-type and mutant C-terminally Bis-tagged enzymes lacking the N-terminal transmembrane helix in Escherichia coli strain JM109 Homo sapiens

Protein Variants

Protein Variants Comment Organism
R347H site-directed mutagenesis, the mutant shows no cytochrome b5-CYP17A1 complex formation Homo sapiens
R358Q site-directed mutagenesis, the mutant shows altered cytochrome b5-CYP17A1 complex formation, CYP17A1 R358Q mutant may interact with cytochrome b5 but clearly not in a way that corresponds to wild-type CYP17A1 binding of cytochrome b5 Homo sapiens
R449L site-directed mutagenesis, the mutant shows no cytochrome b5-CYP17A1 complex formation Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
pregnenolone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
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17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P05093
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-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information cytochrome P450 17A1 is bifunctional and steroidogenic, it performs both steroid hydroxylation, which is unaffected by cytochrome b5, and an androgen-forming lyase reaction, a 17,20-lyase activity, which occurs via a different catalytic mechanism that is facilitated 10fold by cytochrome b5 Homo sapiens ?
-
?
pregnenolone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
pregnenolone + [reduced NADPH-hemoprotein reductase] + O2 via the catalytic cycle involving an iron(IV) oxo intermediate Homo sapiens 17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Synonyms

Synonyms Comment Organism
CYP17A1
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Homo sapiens
cytochrome P450 17A1
-
Homo sapiens

General Information

General Information Comment Organism
additional information substrate-modulated interactions of cytochrome P450 17A1 and cytochrome b5, by reversible binding, involving enzyme anionic residues Glu48 or Glu49 and corresponding cationic CYP17A1 residues Arg347, Arg358, and Arg449, NMR analysis, overview. The CYP17A1/b5 interaction is stronger when the hydroxylase substrate pregnenolone is present in the CYP17A1 active site than when the lyase substrate 17alpha-hydroxypregnenolone is in the active site Homo sapiens
physiological function CYP17A1 plays an essential role in the production of steroid androgens by mediating two subsequent steps in the steroidogenic pathway Homo sapiens