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 | 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 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 | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | heme enzyme | Homo sapiens |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P08686 | - |
- |
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 | Comment | Organism |
---|---|---|
CYP21A2 | - |
Homo sapiens |
cytochrome P450c21 | - |
Homo sapiens |
Progesterone 21-hydroxylase | - |
Homo sapiens |
Steroid 21-hydroxylase | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
heme | - |
Homo sapiens |
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 |