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Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4

  • Amber L. Guidry , Zachary E. Tibbs , Melissa Runge-Morris und Charles N. Falany EMAIL logo
Veröffentlicht/Copyright: 21. Februar 2017
Hormone Molecular Biology and Clinical Investigation
Aus der Zeitschrift Hormone Molecular Biology and Clinical Investigation Band 29 Heft 1

Abstract

Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3′-phosphoadenosine-5′-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate’s biological activity and increasing the compound’s water solubility. While several of the hSULTs’ endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown. The fetal expression of hSULT1C4 leads to the hypothesis that the function of this enzyme may be to regulate metabolic and hormonal signaling molecules, such as estrogenic compounds, that may be generated or consumed by the mother during fetal development. Human SULT1C4 has previously been shown to sulfonate estrogenic compounds, such as catechol estrogens; therefore, this study focused on the expression and purification of hSULT1C4 in order to further characterize this enzyme’s sulfonation of estrogenic compounds. Molecular modeling of the enzyme’s native properties helped to establish a novel purification protocol for hSULT1C4. The optimal activity assay conditions for hSULT1C4 were determined to be pH 7.4 at 37°C for up to 10 min. Kinetic analysis revealed the enzyme’s reduced affinity for PAPS compared to PAP. Human SULT1C4 sulfonated all the estrogenic compounds tested, including dietary flavonoids and environmental estrogens; however, the enzyme has a higher affinity for sulfonation of flavonoids. These results suggest hSULT1C4 could be metabolizing and regulating hormone signaling pathways during human fetal development.

Keywords: estrogen; flavonoids; protein purification; sulfonation; sulfotransferase

  1. Author Statement

  2. Research funding: This work was supported by the National Institutes of Health Grant GM038953 and National Institutes of Health Grant ES022606.

  3. Conflict of interest: The authors have no conflict of interest to report.

  4. Informed consent: Informed consent is not applicable.

  5. Ethical approval: The conducted research is not related to either human or animals use.

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Received: 2016-11-10
Accepted: 2016-12-3
Published Online: 2017-2-21
Published in Print: 2017-1-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Review Article
  3. The evolution of genomic stability to a mechanism in reproduction and psychiatry
  4. Original Articles
  5. 17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression
  6. Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4
  7. Letter to the Editor
  8. Comment on: “Is there a role for vitamin D in human reproduction?”
https://doi.org/10.1515/hmbci-2016-0053
Schlagwörter für diesen Artikel
estrogen; flavonoids; protein purification; sulfonation; sulfotransferase

Artikel in diesem Heft

  1. Frontmatter
  2. Review Article
  3. The evolution of genomic stability to a mechanism in reproduction and psychiatry
  4. Original Articles
  5. 17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression
  6. Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4
  7. Letter to the Editor
  8. Comment on: “Is there a role for vitamin D in human reproduction?”
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