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 3SWZ
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001.
Devore, N.M., Scott, E.E.
Nature