ArticleDrug metabolism and disposition: the biological fate of chemicals2012
Potent inhibition of human sulfotransferase 1A1 by 17α-ethinylestradiol: role of 3'-phosphoadenosine 5'-phosphosulfate binding and structural rearrangements in regulating inhibition and activity.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial.BMC women's health · 2022Trial
- A simple method to measure sulfonation in man using paracetamol as probe drug.Scientific reports · 2021Trial
- Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone-only pill.Acta obstetricia et gynecologica Scandinavica · 2019Trial
- Oral Progestins in Hormonal Contraception: Importance and Future Perspectives of a New Progestin Only-Pill Containing 4 mg Drospirenone.Geburtshilfe und Frauenheilkunde · 2021Article
- Decreased phenol sulfotransferase activities associated with hyperserotonemia in autism spectrum disorders.Translational psychiatry · 2021Article
- The Uptake of Ethinyl-Estradiol and Cortisol From Water by Mussels (Frontiers in endocrinology · 2021Article
- Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism.Scientific reports · 2017Article
- Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4.Hormone molecular biology and clinical investigation · 2017Article
- An engineered heterodimeric model to investigate SULT1B1 dependence on intersubunit communication.Biochemical pharmacology · 2016Article
- Controlling Sulfuryl-Transfer Biology.Cell chemical biology · 2016Article
- Design and Interpretation of Human Sulfotransferase 1A1 Assays.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- Transcript analysis of laser capture microdissected white matter astrocytes and higher phenol sulfotransferase 1A1 expression during autoimmune neuroinflammation.Journal of neuroinflammation · 2015Article
- High accuracy in silico sulfotransferase models.The Journal of biological chemistry · 2013Article
- In silico mechanistic profiling to probe small molecule binding to sulfotransferases.PloS one · 2013Article
- Hormone treatment and UVB exposure influences on female mice regarding skin physiological parameters, biochemical parameters and organ histology.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologieArticle
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5 authors at 3 institutions in 2 countries.
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Abstract
Sulfotransferase (SULT) 1A1 is the major drug/xenobiotic-conjugating SULT isoform in human liver because of its broad substrate reactivity and high expression level. SULT1A1 sulfates estrogens with low micromolar K(m) values consistent with its affinity for sulfation of many small phenolic compounds. Binding studies showed the unexpected ability of 17α-ethinylestradiol (EE2) to bind and inhibit SULT1A1 activity toward p-nitrophenol and β-naphthol at low nanomolar concentrations, whereas EE2 was not sulfated until significantly higher concentrations were reached. EE2 had a K(i) of 10 nM for inhibiting p-nitrophenol and β-naphthol sulfation and inhibited 17β-estradiol (E2) sulfation in intact human MCF-7 breast cancer cells with a K(i) of 19 nM. In contrast, the K(m) for EE2 sulfation by SULT1A1 was 700 nM. The K(d) for EE2 binding of pure SULT1A1 was 0.5 ± 0.15 μM; however, the K(d) for EE2 binding to the SULT1A1-PAP complex was >100-fold lower (4.3 ± 1.7 nM). The K(d) for E2 binding to SULT1A1 changed from 2.3 ± 0.9 to 1.2 ± 0.56 μM in the presence of PAP. Docking studies with E2 indicate that E2 binds in a competent orientation in the resolved structure of SULT1A1 in the both presence and absence of 3'-phosphoadenosine 5'-phosphosulfate (PAPS). However, EE2 binds in a catalytically competent orientation in the absence of PAPS but in a noncompetent orientation via formation of a charge interaction with Tyr108 if PAPS is bound first. In conclusion, EE2 is a potent inhibitor, but not a substrate, of SULT1A1 at low nanomolar concentrations, indicating the possibility of drug-drug interactions during contraceptive therapy.
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