This is an old revision of this page, as edited by Prsbvlp(talk | contribs) at 09:22, 13 August 2020(Add references and minor text). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.
Revision as of 09:22, 13 August 2020 by Prsbvlp(talk | contribs)(Add references and minor text)
Steroid sulfatase (STS), or steryl-sulfatase (EC3.1.6.2), formerly known as arylsulfatase C, is a sulfataseenzyme involved in the metabolism of steroids. It is encoded by the STS gene.[3]
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
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
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 namesteryl-sulfate sulfohydrolase.[13][14][15]
^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. PMID15607112.
Shankaran R, Ameen M, Daniel WL, Davidson RG, Chang PL (June 1991). "Characterization of arylsulfatase C isozymes from human liver and placenta". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1078 (2): 251–7. doi:10.1016/0167-4838(91)90566-I. PMID2065092.
Stein C, Hille A, Seidel J, Rijnbout S, Waheed A, Schmidt B, Geuze H, von Figura K (August 1989). "Cloning and expression of human steroid-sulfatase. Membrane topology, glycosylation, and subcellular distribution in BHK-21 cells". The Journal of Biological Chemistry. 264 (23): 13865–72. PMID2668275.
Kawano J, Kotani T, Ohtaki S, Minamino N, Matsuo H, Oinuma T, Aikawa E (August 1989). "Characterization of rat and human steroid sulfatases". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 997 (3): 199–205. doi:10.1016/0167-4838(89)90187-8. PMID2765556.
Yen PH, Allen E, Marsh B, Mohandas T, Wang N, Taggart RT, Shapiro LJ (May 1987). "Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange". Cell. 49 (4): 443–54. doi:10.1016/0092-8674(87)90447-8. PMID3032454.
Conary JT, Lorkowski G, Schmidt B, Pohlmann R, Nagel G, Meyer HE, Krentler C, Cully J, Hasilik A, von Figura K (April 1987). "Genetic heterogeneity of steroid sulfatase deficiency revealed with cDNA for human steroid sulfatase". Biochemical and Biophysical Research Communications. 144 (2): 1010–7. doi:10.1016/S0006-291X(87)80064-5. PMID3034252.
Ballabio A, Parenti G, Carrozzo R, Coppa G, Felici L, Migliori V, Silengo M, Franceschini P, Andria G (July 1988). "X/Y translocation in a family with X-linked ichthyosis, chondrodysplasia punctata, and mental retardation: DNA analysis reveals deletion of the steroid sulphatase gene and translocation of its Y pseudogene". Clinical Genetics. 34 (1): 31–7. doi:10.1111/j.1399-0004.1988.tb02612.x. PMID3165728.
Yen PH, Marsh B, Allen E, Tsai SP, Ellison J, Connolly L, Neiswanger K, Shapiro LJ (December 1988). "The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: evidence for an inversion of the Y chromosome during primate evolution". Cell. 55 (6): 1123–35. doi:10.1016/0092-8674(88)90257-7. PMID3203382.
Chang PL, Varey PA, Rosa NE, Ameen M, Davidson RG (November 1986). "Association of steroid sulfatase with one of the arylsulfatase C isozymes in human fibroblasts". The Journal of Biological Chemistry. 261 (31): 14443–7. PMID3464600.
Müller CR, Wahlström J, Ropers HH (1982). "Further evidence for the assignment of the steroid sulfatase X-linked ichthyosis locus to the telomer of Xp". Human Genetics. 58 (4): 446–447. doi:10.1007/bf00282842. PMID6948769.
Migeon BR, Shapiro LJ, Norum RA, Mohandas T, Axelman J, Dabora RL (October 1982). "Differential expression of steroid sulphatase locus on active and inactive human X chromosome". Nature. 299 (5886): 838–40. Bibcode:1982Natur.299..838M. doi:10.1038/299838a0. PMID6957717.
Oyama N, Satoh M, Iwatsuki K, Kaneko F (June 2000). "Novel point mutations in the steroid sulfatase gene in patients with X-linked ichthyosis: transfection analysis using the mutated genes". The Journal of Investigative Dermatology. 114 (6): 1195–9. doi:10.1046/j.1523-1747.2000.00004.x. PMID10844566.
Hoffmann R, Rot A, Niiyama S, Billich A (December 2001). "Steroid sulfatase in the human hair follicle concentrates in the dermal papilla". The Journal of Investigative Dermatology. 117 (6): 1342–8. doi:10.1046/j.0022-202x.2001.01547.x. PMID11886493.
Matsuoka R, Yanaihara A, Saito H, Furusawa Y, Toma Y, Shimizu Y, Yanaihara T, Okai T (June 2002). "Regulation of estrogen activity in human endometrium: effect of IL-1beta on steroid sulfatase activity in human endometrial stromal cells". Steroids. 67 (7): 655–9. doi:10.1016/S0039-128X(02)00016-8. PMID11996939.