CATH Classification

Domain Context

CATH Clusters

Superfamily Cytochrome P450
Functional Family Cytochrome P450 1A1

Enzyme Information

1.14.14.19
Steroid 17-alpha-monooxygenase.
based on mapping to UniProt P05093
A C(21)-steroid + [reduced NADPH--hemoprotein reductase] + O(2) = a 17-alpha-hydroxy-C(21)-steroid + [oxidized NADPH--hemoprotein reductase] + H(2)O.
-!- Requires NADPH and EC 1.6.2.4. -!- Catalyzes two independent reactions at the same active site - the 17-alpha-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis, and the conversion of the 17-alpha-hydroxylated products via a 17,20-lyase reaction to form androstenedione and dehydroepiandrosterone, leading to sex hormone biosynthesis (EC 1.14.14.32). -!- The ratio of the 17-alpha-hydroxylase and 17,20-lyase activities is an important factor in determining the directions of steroid hormone biosynthesis toward biosynthesis of glucocorticoid or sex hormones. -!- Formerly EC 1.14.1.7, EC 1.14.99.9 and EC 1.99.1.9.
1.14.14.32
17-alpha-hydroxyprogesterone deacetylase.
based on mapping to UniProt P05093
(1) 17-alpha-hydroxyprogesterone + [reduced NADPH--hemoprotein reductase] + O(2) = androstenedione + acetate + [oxidized NADPH--hemoprotein reductase] + H(2)O. (2) 17-alpha-hydroxypregnenolone + [reduced NADPH--hemoprotein reductase] + O(2) = 3-beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH- -hemoprotein reductase] + H(2)O.
-!- A microsomal protein that catalyzes two independent reactions at the same active site - the 17-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis (EC 1.14.14.19), and the conversion of the 17-hydroxylated products via a 17,20-lyase reaction to form androstenedione and 3-beta- hydroxyandrost-5-en-17-one, leading to sex hormone biosynthesis. -!- The activity of this reaction is dependent on the allosteric interaction of the enzyme with cytochrome b5 without any transfer of electrons from the cytochrome. -!- The enzymes from different organisms differ in their substrate specificity; while the enzymes from pig, hamster, and rat accept both 17-alpha-hydroxyprogesterone and 17-alpha-hydroxypregnenolone, the enzymes from human, bovine, sheep, goat, and bison do not accept the former, and the enzyme from guinea pig does not accept the latter. -!- Formerly EC 4.1.2.30.

UniProtKB Entries (1)

P05093
CP17A_HUMAN
Homo sapiens
Steroid 17-alpha-hydroxylase/17,20 lyase

PDB Structure

PDB 6CIZ
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.
Fehl, C., Vogt, C.D., Yadav, R., Li, K., Scott, E.E., Aube, J.
J. Med. Chem.
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