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Literature summary for 1.14.14.16 extracted from

  • Mizrachi, D.; Wang, Z.; Sharma, K.K.; Gupta, M.K.; Xu, K.; Dwyer, C.R.; Auchus, R.J.
    Why human cytochrome P450c21 is a progesterone 21-hydroxylase (2011), Biochemistry, 50, 3968-3974.
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
I471A site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme Homo sapiens
I471G site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme Homo sapiens
L107X site-directed mutagenesis, inactive mutant Homo sapiens
L109X site-directed mutagenesis, inactive mutant Homo sapiens
V359A site-directed mutagenesis, the mutant shows 60% reduced activity compared to the wild-type enzyme Homo sapiens
V359G site-directed mutagenesis, the mutant shows 10% reduced activity compared to the wild-type enzyme Homo sapiens
V470A site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme Homo sapiens
V470A/I471A site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme Homo sapiens
V470G site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information no inhibition of progesterone 21-hydroxylation by the wild-type enzyme by pregnenolone, 17alpha-hydroxypregnenolone, and 5alpha-pregnane-3alpha-ol-20-one (allopregnanolone) Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00048
-
progesterone pH 7.4, 37°C, mutant V359A Homo sapiens
0.00061
-
17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V359G Homo sapiens
0.00082
-
17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V359A Homo sapiens
0.001
-
progesterone pH 7.4, 37°C, mutant V470A Homo sapiens
0.0011
-
progesterone pH 7.4, 37°C, wild-type enzyme Homo sapiens
0.0015
-
progesterone pH 7.4, 37°C, mutant V470A/I471A Homo sapiens
0.0016
-
17alpha-hydroxyprogesterone pH 7.4, 37°C, wild-type enzyme Homo sapiens
0.0016
-
17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V470A/I471A Homo sapiens
0.0025
-
17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V470A Homo sapiens
0.0032
-
progesterone pH 7.4, 37°C, mutant V359G Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ heme enzyme Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
progesterone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P08686
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2 preferred substrate. The 17alpha-hydroxyprogesterone metabolites formed by mutants of V470 and I471 include a second, unidentified product. Both mutants V359A and V359G also metabolize 17alpha-hydroxyprogesterone to 11-deoxycortisol and this second product, and for mutation V359G, the unidentified compound is the major product. The second compound is not androstenedione and is neither the 16alpha- nor 6beta-hydroxylation products (pregn-4-ene-16alpha,17alpha-diol-3,20-dione and pregn-4-ene-6beta,17alpha-diol-3,20-dione, respectively) Homo sapiens 11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
additional information 17alpha-hydroxyprogesterone is hydroxylated 28times faster than progesterone by the wild-type enzyme. No activity of the wild-type enzyme with pregnenolone, 17alpha-hydroxypregnenolone, and 5alpha-pregnane-3alpha-ol-20-one (allopregnanolone) Homo sapiens ?
-
?
progesterone + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
progesterone + [reduced NADPH-hemoprotein reductase] + O2 mutants V359A and V359G both produce an additional metabolite, 16alpha-hydroxyprogesterone Homo sapiens 16alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O product identification by TLC ?

Synonyms

Synonyms Comment Organism
CYP21A2
-
Homo sapiens
cytochrome P450c21
-
Homo sapiens
Progesterone 21-hydroxylase
-
Homo sapiens
Steroid 21-hydroxylase
-
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

Cofactor

Cofactor Comment Organism Structure
heme
-
Homo sapiens

General Information

General Information Comment Organism
additional information residues L107, L109, V470, I471, and V359 contribute to the CYP21A2 substrate-binding pocket. Progesterone binds to CYP21A2 in a fundamentally different orientation than to CYP17A1, EC 1.14.99.9, expansion of the CYP21A2 substrate-binding pocket allows additional substrate trajectories and metabolic switching. CYP21A2 structure modelling, overview Homo sapiens
physiological function CYP21A2 activities are required for cortisol and aldosterone biosynthesis, and involve the formation of energetically disfavored primary carbon radicals Homo sapiens