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Literature summary extracted from
- Structural insights into aldosterone synthase substrate specificity and targeted inhibition (2013), Mol. Endocrinol., 27, 315-324.
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 1.14.15.4 | drug development | the enzyme is a target for development of selective and potent CYP11B2 inhibitors | Homo sapiens |
| 1.14.15.4 | medicine | blocking of aldosterone synthesis by mediating aldosterone synthase activity is a possible pharmacological therapy for hypertension | Homo sapiens |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.14.15.4 | expression of mature form of CYP11B1 protein without the mitochondrial targeting peptide and with N-terminal tag MAKKTSS added to the 26th residue of CYP11B1, and with C-terminal His6-tag, coexpression with GroEL/ES in Escherichia coli strain JM109 | Homo sapiens |
| 1.14.15.4 | expression of mature form of CYP11B2 protein without the mitochondrial targeting peptide and with N-terminal tag MAKKTSS added to the 30th residue of CYP11B2, and with C-terminal His6-tag, coexpression with GroEL/ES in Escherichia coli strain JM109 | Homo sapiens |
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 1.14.15.4 | purified recombinant N-terminally MAKKTSS-tagged and C-terminally His6-tagged CYP11B2 without mitochondrial targeting peptide complexed with substrate or inhibitor, hanging drop vapor diffusion method, 14 mg/ml protein in 50 mM potassium phosphate, pH 7.4, containing 500 mM NaCl, 0.5% CHAPS, 20% glycerol, and 0.05 mM 11-deoxycortisosterone or 0.05 mM fadrozole, mixing with reservoir solution containing 10% PEG 4000, 0.2 M lithium sulfate, and 0.1 M Tris, pH 8.5, X-ray diffraction structure determination and analysis at 2.5-2.7 A resolution | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.15.4 | fadrozole | isoform-selective inhibitor binding. Fadrozole binds to aldosterone synthase in the R-configuration, using part of the active site cavity pointing toward the egress channel | Homo sapiens |  |
| 1.14.15.4 | additional information | structure homology modelling for inhibitor design, overview | Homo sapiens |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.15.4 | 11-deoxycorticosterone + reduced adrenodoxin + O2 | Homo sapiens | - |
corticosterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | corticosterone + reduced adrenodoxin + O2 | Homo sapiens | - |
18-hydroxycorticosterone + oxidized adrenodoxin + H2O | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.14.15.4 | Homo sapiens | P15538 | - |
- |
| 1.14.15.4 | Homo sapiens | P19099 | - |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 1.14.15.4 | recombinant mature form of C-terminally His6-tagged CYP11B1 from Escherichia coli strain JM109 by nickel affinity and cation exchange chromatography to homogeneity | Homo sapiens |
| 1.14.15.4 | recombinant mature form of C-terminally His6-tagged CYP11B2 from Escherichia coli strain JM109 by nickel affinity and cation exchange chromatography to homogeneity | Homo sapiens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.15.4 | 11-deoxycorticosterone + reduced adrenodoxin + O2 | - |
Homo sapiens | corticosterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | 11-deoxycorticosterone + reduced adrenodoxin + O2 | i.e. 21-hydroxyprogesterone | Homo sapiens | corticosterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | 11-deoxycortisol + reduced adrenodoxin + O2 | - |
Homo sapiens | cortisol + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | androstendione + reduced adrenodoxin + O2 | low activity with isozyme CYP11B1 | Homo sapiens | ? + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | androstendione + reduced adrenodoxin + O2 | low activity with isozyme CYP11B2 | Homo sapiens | ? + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | corticosterone + reduced adrenodoxin + O2 | - |
Homo sapiens | 18-hydroxycorticosterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | additional information | aldosterone synthase shows high 11beta-hydroxylase activity toward both gluco- and mineralocorticoid formation, and additional 18-oxidase activity, substrate specificties of isozymes CYP11B2 and CYP11B1, overview. No oxidation activity of CYP11B2 with 18-hydroxycorticosterone, 11-dehydrocorticosterone, 21-hydroxypregnenolone, and poor activity with cortisol | Homo sapiens | ? | - |
? | |
| 1.14.15.4 | additional information | substrate specificties of isozymes CYP11B2 and CYP11B1, overview. No or poor activity of CYP11B1 with cortisol, 18-hydroxycorticosterone, 11-dehydrocorticosterone, 21-hydroxypregnenolone, and 11beta-hydroxyprogesterone | Homo sapiens | ? | - |
? | |
| 1.14.15.4 | progesterone + reduced adrenodoxin + O2 | low activity with isozyme CYP11B1 | Homo sapiens | 11beta-hydroxyprogesterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | progesterone + reduced adrenodoxin + O2 | low activity with isozyme CYP11B2 | Homo sapiens | 11beta-hydroxyprogesterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | testosterone + reduced adrenodoxin + O2 | low activity with isozyme CYP11B1 | Homo sapiens | 11-hydroxytestosterone + oxidized adrenodoxin + H2O | - |
? | |
| 1.14.15.4 | testosterone + reduced adrenodoxin + O2 | low activity with isozyme CYP11B2 | Homo sapiens | 11-hydroxytestosterone + oxidized adrenodoxin + H2O | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.14.15.4 | Aldosterone synthase | - |
Homo sapiens |
| 1.14.15.4 | CYP11B1 | - |
Homo sapiens |
| 1.14.15.4 | CYP11B2 | - |
Homo sapiens |
| 1.14.15.4 | cytochrome P450 11B1 | - |
Homo sapiens |
| 1.14.15.4 | cytochrome P450 11B2 | - |
Homo sapiens |
Temperature Optimum [°C]
| EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|---|
| 1.14.15.4 | 37 | - |
assay at | Homo sapiens |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.14.15.4 | 7.2 | - |
assay at | Homo sapiens |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.15.4 | adrenodoxin | - |
Homo sapiens |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.14.15.4 | evolution | although the active site pocket is lined by identical residues between CYP11B isoforms, most of the divergent residues that confer additional 18-oxidase activity of aldosterone synthase are located in the I-helix, vicinity of the O2 activation path and loops around the H-helix, affecting an egress channel closure required for retaining intermediates in the active site | Homo sapiens |
| 1.14.15.4 | additional information | a hydrophobic cavity with specific features is associated with corticosteroid recognition, substrate binding mode, overview | Homo sapiens |
| 1.14.15.4 | physiological function | aldosterone synthase, CYP11B2, is the sole enzyme responsible for the production of aldosterone in humans | Homo sapiens |
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Release 2023.1 (January 2023)
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