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Identification of new probe substrates for human CYP20A1

  • Pradeepraj Durairaj , Linbing Fan , Sangeeta Shrestha Sharma , Zhao Jie und Matthias Bureik EMAIL logo
Veröffentlicht/Copyright: 28. Oktober 2019
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 401 Heft 3

Abstract

CYP20A1 is a well-conserved member of the human cytochrome P450 enzyme family for which no endogenous or xenobiotic substrate is known. We have recently shown that this enzyme has moderate activity towards two proluciferin probe substrates. In order to facilitate the search for physiological substrates we have tested nine additional proluciferins in this study and identified three such probe substrates that give much higher product yields. Using one of these probes, we demonstrate inhibition of CYP20A1 activity by 1-benzylimidazole, ketoconazole and letrozole. Finally, we show that the combination of two common single nucleotide polymorphisms (SNPs) of CYP20A1 leads to an enzyme (CYP20A1Leu97Phe346) with reduced activity.

Keywords: cytochrome P450; enzyme inhibition; fission yeast; S. pombe; single nucleotide polymorphism

  1. Conflict of interest statement: The authors report no financial or other relationship relevant to the subject of this article.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2019-0307).

Received: 2019-07-05
Accepted: 2019-10-08
Published Online: 2019-10-28
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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  2. Reviews
  3. Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function
  4. Transport mechanism of Mycobacterium tuberculosis MmpL/S family proteins and implications in pharmaceutical targeting
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https://doi.org/10.1515/hsz-2019-0307
Schlagwörter für diesen Artikel
cytochrome P450; enzyme inhibition; fission yeast; S. pombe; single nucleotide polymorphism

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function
  4. Transport mechanism of Mycobacterium tuberculosis MmpL/S family proteins and implications in pharmaceutical targeting
  5. Research Articles/Short Communications
  6. Genes and Nucleic Acids
  7. LncRNA MALAT1 inhibits hypoxia/reoxygenation-induced human umbilical vein endothelial cell injury via targeting the microRNA-320a/RAC1 axis
  8. Protein Structure and Function
  9. Identification of new probe substrates for human CYP20A1
  10. Molecular Medicine
  11. Exosomal MALAT1 derived from ox-LDL-treated endothelial cells induce neutrophil extracellular traps to aggravate atherosclerosis
  12. Cell Biology and Signaling
  13. Derlin-1 functions as a growth promoter in breast cancer
  14. Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting
  15. Long noncoding RNA Linc01296 promotes hepatocellular carcinoma development through regulation of the miR-26a/PTEN axis
  16. Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer
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