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Literature summary 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

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.14.16 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]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.14.14.16 0.00048
-
 progesterone pH 7.4, 37°C, mutant V359A Homo sapiens
1.14.14.16 0.00061
-
 17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V359G Homo sapiens
1.14.14.16 0.00082
-
 17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V359A Homo sapiens
1.14.14.16 0.001
-
 progesterone pH 7.4, 37°C, mutant V470A Homo sapiens
1.14.14.16 0.0011
-
 progesterone pH 7.4, 37°C, wild-type enzyme Homo sapiens
1.14.14.16 0.0015
-
 progesterone pH 7.4, 37°C, mutant V470A/I471A Homo sapiens
1.14.14.16 0.0016
-
 17alpha-hydroxyprogesterone pH 7.4, 37°C, wild-type enzyme Homo sapiens
1.14.14.16 0.0016
-
 17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V470A/I471A Homo sapiens
1.14.14.16 0.0025
-
 17alpha-hydroxyprogesterone pH 7.4, 37°C, mutant V470A Homo sapiens
1.14.14.16 0.0032
-
 progesterone pH 7.4, 37°C, mutant V359G Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.14.16 Fe2+ heme enzyme 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 progesterone + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens
-
 11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.16 Homo sapiens P08686
-
-

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 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
-
 ?
1.14.14.16 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 ?
-
 ?
1.14.14.16 progesterone + [reduced NADPH-hemoprotein reductase] + O2
-
 Homo sapiens 11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.16 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

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

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.14.16 7.4
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.14.16 heme
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.14.14.16 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
1.14.14.16 physiological function CYP21A2 activities are required for cortisol and aldosterone biosynthesis, and involve the formation of energetically disfavored primary carbon radicals Homo sapiens