Steroid sulfatase

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STS
Protein STS PDB 1p49.png
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesSTS, ARSC, ARSC2, ARSC1, ASC, ES, SSDD, XLI, Steroid sulfatase (microsomal), isozyme S, steroid sulfatase
External IDsOMIM: 300747 HomoloGene: 47918 GeneCards: STS
Gene location (Human)
X chromosome (human)
Chr.X chromosome (human)[1]
X chromosome (human)
Genomic location for STS
Genomic location for STS
BandXp22.31Start7,147,237 bp[1]
End7,804,358 bp[1]
RNA expression pattern
PBB GE STS 203769 s at fs.png

PBB GE STS 203768 s at fs.png

PBB GE STS 203767 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr X: 7.15 – 7.8 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human
Steryl-sulfatase
Identifiers
EC number3.1.6.2
CAS number9025-62-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

Steroid sulfatase (STS), or steryl-sulfatase (EC 3.1.6.2), formerly known as arylsulfatase C, is a sulfatase enzyme involved in the metabolism of steroids. It is encoded by the STS gene.[3]

Reactions[edit]

This enzyme catalyses the following chemical reaction

3β-hydroxyandrost-5-en-17-one 3-sulfate + H2O 3β-hydroxyandrost-5-en-17-one + sulfate

Also acts on some related steryl sulfates.

Function[edit]

The protein encoded by this gene catalyzes the conversion of sulfated steroid precursors to the free steroid. This includes DHEA sulfate, estrone sulfate, pregnenolone sulfate, and cholesterol sulfate, all to their unconjugated forms (DHEA, estrone, pregnenolone, and cholesterol, respectively).[4][5] The encoded protein is found in the endoplasmic reticulum, where it is present as a homodimer.[3]

Distribution of STS and EST activities for interconversion of estrone (E1) and estrone sulfate (E1S) in adult human tissues.[6]

Clinical significance[edit]

A congenital deficiency in the enzyme is associated with X-linked ichthyosis, a scaly-skin disease affecting roughly 1 in every 2,000 to 6,000 males.[7][8] The excessive skin scaling or hyperkeratosis is caused by a lack of breakdown and thus accumulation of cholesterol sulfate, a steroid that stabilizes cell membranes and adds cohesion, in the outer layers of the skin.[4]

Steroid sulfates like DHEA sulfate and estrone sulfate serve as large biologically inert reservoirs for conversion into androgens and estrogens, respectively, and hence are of significance for androgen- and estrogen-dependent conditions like prostate cancer, breast cancer, endometriosis, and others. A number of clinical trials have been performed with inhibitors of the enzyme that have demonstrated clinical benefit, particularly in oncology and so far up to Phase II.[9] The non-steroidal drug Irosustat has been the most studied to date.

Inhibitors[edit]

Inhibitors of STS include irosustat, estrone sulfamate (EMATE), estradiol sulfamate (E2MATE), and danazol.[10][11] The most potent inhibitors are based around the aryl sulfamate pharmacophore[12] and it is thought that such compounds irreversibly modify the active site formylglycine residue of steroid sulfatase.[9]

Names[edit]

Steryl-sulfatase is also known as arylsulfatase, steroid sulfatase, sterol sulfatase, dehydroepiandrosterone sulfate sulfatase, arylsulfatase C, steroid 3-sulfatase, steroid sulfate sulfohydrolase, dehydroepiandrosterone sulfatase, pregnenolone sulfatase, phenolic steroid sulfatase, 3-beta-hydroxysteroid sulfate sulfatase, as well as by its systematic name steryl-sulfate sulfohydrolase.[13][14][15]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000101846 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b "Entrez Gene: STS steroid sulfatase (microsomal), arylsulfatase C, isozyme S".
  4. ^ a b Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA (October 2015). "The Regulation of Steroid Action by Sulfation and Desulfation". Endocrine Reviews. 36 (5): 526–63. doi:10.1210/er.2015-1036. PMC 4591525. PMID 26213785.
  5. ^ Rižner TL (2016). "The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases". Frontiers in Pharmacology. 7: 30. doi:10.3389/fphar.2016.00030. PMC 4757672. PMID 26924986.
  6. ^ Miki Y, Nakata T, Suzuki T, Darnel AD, Moriya T, Kaneko C, Hidaka K, Shiotsu Y, Kusaka H, Sasano H (December 2002). "Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues". J. Clin. Endocrinol. Metab. 87 (12): 5760–8. doi:10.1210/jc.2002-020670. PMID 12466383.
  7. ^ Alperin ES, Shapiro LJ (August 1997). "Characterization of point mutations in patients with X-linked ichthyosis. Effects on the structure and function of the steroid sulfatase protein". The Journal of Biological Chemistry. 272 (33): 20756–63. doi:10.1074/jbc.272.33.20756. PMID 9252398.
  8. ^ Ghosh D (December 2004). "Mutations in X-linked ichthyosis disrupt the active site structure of estrone/DHEA sulfatase". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1739 (1): 1–4. doi:10.1016/j.bbadis.2004.09.003. PMID 15607112.
  9. ^ a b Potter, BVL (2018). "SULFATION PATHWAYS: Steroid Sulfatase Inhibition by Aryl Sulfamates: Clinical Progress, Mechanism, and Future Prospects". J Mol Endocrinol. 61(2): T233–T252.
  10. ^ Thomas MP, Potter BV (2015). "Estrogen O-sulfamates and their analogues: Clinical steroid sulfatase inhibitors with broad potential". J. Steroid Biochem. Mol. Biol. 153: 160–9. doi:10.1016/j.jsbmb.2015.03.012. PMID 25843211.
  11. ^ Carlström K, Döberl A, Pousette A, Rannevik G, Wilking N (1984). "Inhibition of steroid sulfatase activity by danazol". Acta Obstet Gynecol Scand Suppl. 123: 107–11. doi:10.3109/00016348409156994. PMID 6238495.
  12. ^ Thomas, MP, Potter BVL (2015). "Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women's Health". J. Med. Chem. 58(19): 7634–7658.
  13. ^ Roy AB (October 1954). "The steroid sulphatase of Patella vulgata". Biochimica et Biophysica Acta. 15 (2): 300–1. doi:10.1016/0006-3002(54)90078-5. PMC 1274509. PMID 13208702.
  14. ^ Roy AB (1960). The synthesis and hydrolysis of sulfate esters. Advances in Enzymology and Related Subjects of Biochemistry. Advances in Enzymology - and Related Areas of Molecular Biology. 22. pp. 205–35. doi:10.1002/9780470122679.ch5. ISBN 9780470122679. PMID 13744184.
  15. ^ Halkerston ID, Hillman J, Stitch SR (August 1956). "The enzymic hydrolysis of steroid conjugates. I. Sulphatase and beta-glucuronidase activity of molluscan extracts". The Biochemical Journal. 63 (4): 705–10. doi:10.1042/bj0630705. PMC 1216242. PMID 13355874.

Further reading[edit]

External links[edit]