Steroid 17-alpha-hydroxylase/17,20 lyase

UniProt P05093 Organism Homo sapiens Gene CYP17, CYP17A1, S17AH EC 1.14.14.19, 1.14.14.32

Also known as: CYP17, CYP17A1, S17AH

Function

A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis. Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione. Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

Classification

Family (Pfam): PF00067 p450
InterPro: Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 17

3RUK X-ray 2.60A
3SWZ X-ray 2.40A
4NKV X-ray 2.65A
4NKW X-ray 2.50A
4NKX X-ray 2.79A
4NKY X-ray 2.55A
4NKZ X-ray 3.00A
5IRQ X-ray 2.20A
5IRV X-ray 3.10A
5UYS X-ray 2.39A
6CHI X-ray 2.70A
6CIR X-ray 2.65A
… and 5 more

A predicted model is available from AlphaFold.

Gene Ontology · 17

Disease associations

congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency MONDO:0008730

Drugs targeting this protein · 6

ORTERONEL inhibitor
GALETERONE inhibitor
ABIRATERONE inhibitor
ABIRATERONE ACETATE inhibitor
LEVOKETOCONAZOLE inhibitor
SEVITERONEL inhibitor

Neighborhood · nearest proteins

Nearest neighbours of Steroid 17-alpha-hydroxylase/17,20 lyase: 3 by sequence/function similarity (left); 2 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Steroid 17-alpha-hydroxylase/17,20 lyase 1 shared papers
Steroid 17-alpha-hydroxylase/17,20 lyase 1 shared papers

Literature · 31 cited papers

Hydroxylation and lyase reactions of steroids catalyzed by mouse cytochrome P450 17A1 (Cyp17a1). J. Inorg. Biochem. · 2023
Mechanism of 17alpha,20-Lyase and New Hydroxylation Reactions of Human Cytochrome P450 17A1: 18O LABELING AND OXYGEN SURROGATE EVIDENCE FOR A ROLE OF A PERFERRYL OXYGEN. J. Biol. Chem. · 2016
Partial deficiency of 17alpha-hydroxylase/17,20-lyase caused by a novel missense mutation in the canonical cytochrome heme-interacting motif. Eur. J. Endocrinol. · 2015
Structures of human steroidogenic cytochrome P450 17A1 with substrates. J. Biol. Chem. · 2014
Congenital adrenal hyperplasia due to 17-alpha-hydoxylase/17,20-lyase deficiency presenting with hypertension and pseudohermaphroditism: first case report from Oman. Oman Med. J. · 2014
A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency, a case series of such mutations among Koreans and functional characteristics of a novel mutation. Metabolism · 2014
Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature · 2012
Novel CYP17A1 mutation in a Japanese patient with combined 17alpha-hydroxylase/17,20-lyase deficiency. Metabolism · 2010
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping. J. Clin. Endocrinol. Metab. · 2003
Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency. J. Clin. Endocrinol. Metab. · 2002
… and 19 more in the literature graph

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