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Literature summary for 1.14.14.19 extracted from

  • Khatri, Y.; Gregory, M.C.; Grinkova, Y.V.; Denisov, I.G.; Sligar, S.G.
    Active site proton delivery and the lyase activity of human CYP17A1 (2014), Biochem. Biophys. Res. Commun., 443, 179-184.
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
T306A site-directed mutagenesis, the mutant shows highly reduced hydroxylation activity compared to the wild-type enzyme. due to a high degree of uncoupling in which reducing equivalents and protons are funneled into non-productive pathways. The catalysis of carbon-carbon bond scission by the T306A mutant is largely unimpeded by disruption of the CYP17A1 acid-alcohol pair Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the multifunctional enzyme catalyzes the 17alpha-hydroxylation of DELTA4- and DELTA5-steroids progesterone and pregnenolone to form the corresponding 17alpha-hydroxy products through its hydroxylase activity, and a subsequent 17,20-carbon-carbon scission of pregnene-side chain produce the androgens androstenedione and dehydroepiandrosterone ?
-
?
pregnenolone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
progesterone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P05093
-
-

Reaction

Reaction Comment Organism Reaction ID
a C21-steroid + [reduced NADPH-hemoprotein reductase] + O2 = a 17alpha-hydroxy-C21-steroid + [oxidized NADPH-hemoprotein reductase] + H2O the hydroxylation reaction is believed to proceed through a conventional Compound I rebound mechanism. Thr306 is a member of the conserved acid/alcohol pair essential for the efficient delivery of protons required for hydroperoxoanion heterolysis and formation of Compound I in the cytochromes P450. Involvement of a nucleophilic peroxo-anion rather than the traditional Compound I in catalysis. The peroxoanion is required to initiate O-O bond scission and formation of the Cpd I reactive intermediate Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the multifunctional enzyme catalyzes the 17alpha-hydroxylation of DELTA4- and DELTA5-steroids progesterone and pregnenolone to form the corresponding 17alpha-hydroxy products through its hydroxylase activity, and a subsequent 17,20-carbon-carbon scission of pregnene-side chain produce the androgens androstenedione and dehydroepiandrosterone Homo sapiens ?
-
?
pregnenolone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
pregnenolone + [reduced NADPH-hemoprotein reductase] + O2 via Compound I intermediate Homo sapiens 17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
progesterone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
progesterone + [reduced NADPH-hemoprotein reductase] + O2 via Compound I intermediate Homo sapiens 17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Synonyms

Synonyms Comment Organism
CYP17A1
-
Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

General Information

General Information Comment Organism
metabolism cytochrome P450 CYP17A1 catalyzes a series of reactions that lie at the intersection of corticoid and androgen biosynthesis and thus occupies an essential role in steroid hormone metabolism Homo sapiens