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Literature summary extracted from

  • Sushko, T.A.; Gilep, A.A.; Usanov, S.A.
    Mechanism of intermolecular interactions of microsomal cytochrome P450s CYP17 and CYP21 involved in steroid hormone biosynthesis (2012), Biochemistry (Moscow), 77, 585-592.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.14.19 CYP21 direct molecular interactions, with electrostatic interactions playing a crucial role, between steroidogenic enzymes CYP17 and CYP21, EC 1.14.99.10, that are localized in endoplasmic reticulum membranes of adrenal cortex and involved in biosynthesis of corticosteroid hormones. The interaction in vitro reduces the catalytic activities of both enzymes at high ionic strength, i.e. 300 mM NaCl, while it increases activity at low ionic strength, i.e. 100 mM NaCl, overview Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.14.16 expression of His-tagged enzyme in Escherichia coli strain JM109, coexpression with molecular chaperones GroES and GroEL Homo sapiens
1.14.14.19 expression of His-tagged enzyme in Escherichia coli strain JM109, coexpression with molecular chaperones GroES and GroEL Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.14.19 CYP21 direct molecular interactions, with electrostatic interactions playing a crucial role, between steroidogenic enzymes CYP17 and CYP21, EC 1.14.99.10, that are localized in endoplasmic reticulum membranes of adrenal cortex and involved in biosynthesis of corticosteroid hormones. The interaction in vitro reduces the catalytic activities of both enzymes at high ionic strength, i.e. 300 mM NaCl, while it increases activity at low ionic strength, i.e. 100 mM NaCl, overview Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.14.14.16 endoplasmic reticulum membrane
-
Homo sapiens 5789
-
1.14.14.19 endoplasmic reticulum membrane
-
Homo sapiens 5789
-
1.14.14.19 microsome
-
Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.14.16 17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.16 progesterone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.19 7-dehydropregnenolone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
7-dehydro-17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.19 additional information Homo sapiens CYP17 is unique due to its ability to catalyze two independent reactions in the same active center, the 17alpha-hydroxylase and 17,20-lyase reactions ?
-
?
1.14.14.19 pregnenolone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.19 progesterone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.16 Homo sapiens
-
-
-
1.14.14.19 Homo sapiens P05093
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.14.14.16 recombinant His-tagged enzyme from Escherichia coli strain JM109 by nickel affinity chromatography Homo sapiens
1.14.14.19 recombinant His-tagged enzyme from Escherichia coli strain JM109 by nickel affinity chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.14.19 adrenal cortex
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.14.16 17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.16 progesterone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.19 7-dehydropregnenolone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 7-dehydro-17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.19 additional information CYP17 is unique due to its ability to catalyze two independent reactions in the same active center, the 17alpha-hydroxylase and 17,20-lyase reactions Homo sapiens ?
-
?
1.14.14.19 pregnenolone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 17alpha-hydroxypregnenolone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
1.14.14.19 progesterone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 17alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Subunits

EC Number Subunits Comment Organism
1.14.14.19 More modeling of tertiary structure of CYP17, overview Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.14.14.16 CYP21
-
Homo sapiens
1.14.14.19 17alphahydroxylase
-
Homo sapiens
1.14.14.19 CYP17
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.14.14.16 37
-
assay at Homo sapiens
1.14.14.19 37
-
assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.14.16 7.2
-
assay at Homo sapiens
1.14.14.19 7.2
-
assay at Homo sapiens

General Information

EC Number General Information Comment Organism
1.14.14.16 physiological function CYP21 catalyses reactions of progesterone and 17alpha-hydroxyprogesterone conversion to 11-deoxycorticosterone and 11-deoxycortisol, respectively, providing an important step in aldosterone and cortisol biosynthesis. Direct molecular interactions, with electrostatic interactions playing a crucial role, between steroidogenic enzymes CYP17, EC 1.14.99.9, and CYP21 that are localized in endoplasmic reticulum membranes of adrenal cortex and involved in biosynthesis of corticosteroid hormones. The interaction in vitro reduces the catalytic activities of both enzymes at high ionic strength, i.e. 300 mM NaCl, while it increases activity at low ionic strength, i.e. 100 mM NaCl, overview Homo sapiens
1.14.14.19 metabolism cytochrome b5 plays an important role in the intracellular regulation of biosynthesis of androgens at the level of CYP17. Cytochrome b5 mainly stimulates 17,20-lyase activity of CYP17, but has no effect on the 17alpha-hydroxylation reaction Homo sapiens
1.14.14.19 additional information modeling of tertiary structure of CYP17, overview. Direct molecular interactions, with electrostatic interactions playing a crucial role, between steroidogenic enzymes CYP17 and CYP21 that are localized in endoplasmic reticulum membranes of adrenal cortex and involved in biosynthesis of corticosteroid hormones, overview Homo sapiens
1.14.14.19 physiological function cytochrome CYP17 is a key enzyme of steroid hormone biosynthesis. Bifunctional CYP17 catalyzes two independent reactions in the same active center, the 17alpha-hydroxylase and 17,20-lyase reactions Homo sapiens