Inactivation of steroid sulfatase by an active site-directed inhibitor, estrone-3-O-sulfamate

Biochemistry
Atul PurohitM J Reed

Abstract

Steroid sulfatases are responsible for the hydrolysis of 3beta-hydroxy steroid sulfates, such as cholesterol and pregnenolone sulfate, and have an important role in regulating the synthesis of estrogenic steroids, from estrone sulfate and dehydroepiandrosterone sulfate, in endocrine-dependent tumors. Although little is known about the mechanism by which the sulfate group is removed from a steroid nucleus, an active site-directed sulfatase inhibitor has been developed. This inhibitor, estrone-3-O-sulfamate (EMATE), was synthesized by treating the sodium salt of estrone with sulfamoyl chloride. This compound inhibited not only estrone sulfatase but also dehydroepiandrosterone sulfatase activity in placental microsomes and in intact MCF-7 breast cancer cells. Pretreatment of MCF-7 cells or placental microsomes with EMATE, followed by extensive washing or dialysis indicated irreversible inhibition. This was confirmed by showing that EMATE inhibited estrone sulfatase activity in placental microsomes in a time-, concentration-, and pH-dependent manner. The enzyme is protected from inactivation by estrone sulfate, which is also consistent with active site-directed inhibition. EMATE is proposed to inactivate estrone sulfatase by irreve...Continue Reading

Citations

Nov 25, 2000·Breast Cancer : the Journal of the Japanese Breast Cancer Society·T UtsumiN Harada
Jan 17, 2002·Archives of Pharmacal Research·K P Bhat, J M Pezzuto
Feb 3, 2007·Breast Cancer Research and Treatment·Louise M RasmussenAnne E Lykkesfeldt
Aug 1, 1996·The Journal of Steroid Biochemistry and Molecular Biology·M I Hidalgo AragonesM J Reed
Mar 30, 2004·Biochemical and Biophysical Research Communications·Julie E ReedBarry V L Potter
Oct 14, 2003·Bioorganic & Medicinal Chemistry Letters·Peter NussbaumerAndreas Billich
Dec 4, 2003·Bioorganic & Medicinal Chemistry Letters·Erwin P SchreinerAndreas Billich
May 3, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Mathew P LeeseBarry V L Potter
May 3, 2005·The Journal of Steroid Biochemistry and Molecular Biology·B RaobaikadyM J Reed
May 3, 2005·The Journal of Steroid Biochemistry and Molecular Biology·T UtsumiM J Reed
Dec 12, 2002·Steroids·Richard H PetersMasato Tanabe
Apr 1, 1997·Steroids·N M HowarthB V Potter
Aug 5, 2000·The Journal of Steroid Biochemistry and Molecular Biology·T UtsumiN Harada
Jun 1, 2001·The Journal of Steroid Biochemistry and Molecular Biology·G S Chetrite, J R Pasqualini
May 2, 2002·The Journal of Steroid Biochemistry and Molecular Biology·Sabbir AhmedLuther Sampson
May 2, 2002·The Journal of Steroid Biochemistry and Molecular Biology·Sabbir AhmedChirag K Patel
Feb 19, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Sabbir AhmedCaroline P Owen
Apr 25, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Delphine S FischerBarry V L Potter
Apr 25, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Bindumalini RaobaikadyMichael J Reed
Nov 19, 2003·The Journal of Steroid Biochemistry and Molecular Biology·A PurohitM J Reed
Sep 1, 1996·The Journal of Steroid Biochemistry and Molecular Biology·P K LiM E Rhodes
Feb 4, 1998·The Journal of Steroid Biochemistry and Molecular Biology·Z HuangL S Kaminsky
Apr 24, 1999·The Journal of Steroid Biochemistry and Molecular Biology·A KolliP K Li
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·A PurohitM J Reed
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·J R Pasqualini, G S Chetrite
May 7, 2002·Bioorganic & Medicinal Chemistry Letters·Sabbir AhmedChirag K Patel
Jul 20, 2002·Bioorganic & Medicinal Chemistry Letters·Peter NussbaumerAndreas Billich
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·D Poirier, R P Boivin
Feb 18, 1999·Bioorganic & Medicinal Chemistry Letters·G H ChuP K Li
Jul 9, 1999·Bioorganic & Medicinal Chemistry Letters·S Ahmed, K James
Mar 28, 2003·Bioorganic & Medicinal Chemistry·Delphine S FischerBarry V L Potter
Aug 24, 2011·The Journal of Endocrinology·Atul Purohit, Paul A Foster
May 16, 2014·Endocrine-related Cancer·Trevor M Penning

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.