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Literature summary for 1.14.14.19 extracted from

  • Petrunak, E.M.; DeVore, N.M.; Porubsky, P.R.; Scott, E.E.
    Structures of human steroidogenic cytochrome P450 17A1 with substrates (2014), J. Biol. Chem., 289, 32952-32964.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli JM109 cells Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
mutant enzyme A105L in complex with progesterone, pregnenolone, 17alpha-hydroxypregnenolone, or abiraterone is crystallized by the hanging drop vapor diffusion method using 100 mM Tris-HCl, pH 8.5, 25% (w/v) PEG 4000, 150 mM magnesium chloride hexahydrate, and 4-6% (v/v) glycerol. Mutant enzyme A105L in complex with 17alpha-hydroxyprogesterone is crystallized by the hanging drop vapor diffusion method using 175 mM Tris-HCl, pH 8.5, 30% (w/v) PEG 3350, 250 mM lithium sulfate, and 3% (v/v) glycerol Homo sapiens

Protein Variants

Protein Variants Comment Organism
A105L the effect of the A105L mutation is to increase progesterone affinity at least 2fold but the mutant has little effect on the already lower affinity for either progesterone hydroxylation product Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
abiraterone
-
Homo sapiens
TOK-001
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00038
-
pregnenolone mutant enzyme A105L, at pH 7.4 and 37°C Homo sapiens
0.00093
-
pregnenolone wild type enzyme, at pH 7.4 and 37°C Homo sapiens
0.00196
-
progesterone mutant enzyme A105L, at pH 7.4 and 37°C Homo sapiens
0.0105
-
progesterone wild type enzyme, at pH 7.4 and 37°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
a C21-steroid + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
a 17alpha-hydroxy-C21-steroid + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
additional information Homo sapiens a minor conformation may yield the minor 16alpha-hydroxyprogesterone metabolite from progesterone ?
-
?
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
-
-

Purification (Commentary)

Purification (Comment) Organism
nickel-nitrilotriacetic acid-agarose resin column chromatography, carboxymethyl-Sepharose column chromatography, and Superdex 200 gel filtration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
a C21-steroid + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens a 17alpha-hydroxy-C21-steroid + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
additional information a minor conformation may yield the minor 16alpha-hydroxyprogesterone metabolite from progesterone Homo sapiens ?
-
?
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
-
?

Synonyms

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

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0065
-
pregnenolone wild type enzyme, at pH 7.4 and 37°C Homo sapiens
0.0065
-
pregnenolone mutant enzyme A105L, at pH 7.4 and 37°C Homo sapiens
0.017
-
progesterone wild type enzyme, at pH 7.4 and 37°C Homo sapiens
0.019
-
progesterone mutant enzyme A105L, at pH 7.4 and 37°C Homo sapiens

Cofactor

Cofactor Comment Organism Structure
heme
-
Homo sapiens