CYP17A1

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Cytochrome P450, family 17, subfamily A, polypeptide 1

Human Cytochrome P450 CYP17A1 PDB. 3ruk
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsCYP17A1; CPT7; CYP17; P450C17; S17AH
External IDsOMIM: 609300 MGI: 88586 HomoloGene: 73875 ChEMBL: 3522 GeneCards: CYP17A1 Gene
EC number1.14.99.9
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez158613074
EnsemblENSG00000148795ENSMUSG00000003555
UniProtP05093P27786
RefSeq (mRNA)NM_000102NM_007809
RefSeq (protein)NP_000093NP_031835
Location (UCSC)Chr 10:
104.59 – 104.6 Mb		Chr 19:
46.67 – 46.67 Mb
PubMed search
This box:

Cytochrome P450 17A1, or steroid 17-alpha-monooxygenase, or 17α-hydroxylase/17,20 lyase/17,20 desmolase is an enzyme that in humans is encoded by the CYP17A1 gene. It is found in the zona reticularis of the adrenal cortex. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.

More specifically, CYP17A1 acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity), or acts upon 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side-chain off the steroid nucleus (the lyase activity).[1]

Clinical significance

Mutations in this gene are associated with 17 alpha-hydroxylase deficiency, 17 alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia.[2]

The drug abiraterone which is used to treat castration-resistant prostate cancer blocks the biosynthesis of androgens by inhibiting the CYP17A1 enzyme. Abiterone binds in the active site of the enzyme and coordinates the heme iron through its pyridine nitrogen, mimicking the subtrate.[3]

Steroidogenesis

17α-hydroxylase converts pregnenolone and progesterone to their 17-hydroxy forms, and converts 17-hydroxypregnenolone and 17-hydroxyprogesterone to DHEA and androstenedione, respectively. It corresponds to the downward arrows in this reaction scheme.
Steroidogenesis, showing, at left side, both reactions of 17-alpha hydroxylase, and both actions of 17, 20 lyase.

Additional images

See also

References

  1. ↑ Boulpaep EL, Boron, WF (2005). Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. p. 1180. ISBN 1-4160-2328-3. 
  2. ↑ "Entrez Gene: CYP17A1 cytochrome P450, family 17, subfamily A, polypeptide 1". 
  3. ↑ PDB 3ruk; DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943. 

Further reading

  • Miura K, Yasuda K, Yanase T et al. (1996). "Mutation of cytochrome P-45017 alpha gene (CYP17) in a Japanese patient previously reported as having glucocorticoid-responsive hyperaldosteronism: with a review of Japanese patients with mutations of CYP17". J. Clin. Endocrinol. Metab. 81 (10): 3797–801. doi:10.1210/jc.81.10.3797. PMID 8855840. 
  • Miller WL, Geller DH, Auchus RJ (1999). "The molecular basis of isolated 17,20 lyase deficiency". Endocr. Res. 24 (3–4): 817–25. doi:10.3109/07435809809032692. PMID 9888582. 
  • Strauss JF (2004). "Some new thoughts on the pathophysiology and genetics of polycystic ovary syndrome". Annals of the New York Academy of Sciences 997: 42–8. doi:10.1196/annals.1290.005. PMID 14644808. 
  • Haider S, Patel J, Poojari C, Neidle S (2010). "Molecular modeling on inhibitor complexes and active-site dynamics of cytochrome P450 C17, a target for prostate cancer therapy". J. Mol Biol 400 (5): 1078–098. doi:10.1016/j.jmb.2010.05.069. PMID 20595043. 

External links

1.14.11: 2-oxoglutarate
1.14.13: NADH or NADPH
1.14.14: reduced flavin or flavoprotein
1.14.15: reduced iron-sulfur protein
1.14.16: reduced pteridine (BH4 dependent)
1.14.17: reduced ascorbate
1.14.18-19: other
1.14.99 - miscellaneous
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Metabolism: lipid metabolism – ketones/cholesterol synthesis enzymes/steroid metabolism
Mevalonate pathway
To HMG-CoA
Ketogenesis
To Mevalonic acid
To DMAPP
Geranyl-
To cholesterol
To lanosterol
7-Dehydrocholesterol path
Desmosterol path
To Bile acids
Steroidogenesis
To pregnenolone
To corticosteroids
To sex hormones
To androgens
To estrogens
Other/ungrouped

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

M: END

anat/phys/devp/horm

noco (d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)

CYP1
CYP2
CYP3 (CYP3A)
CYP4
CYP5-20
CYP21-51
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