2. Academic Validation
  3. Initial characterization of human DHRS1 (SDR19C1), a member of the short-chain dehydrogenase/reductase superfamily

Initial characterization of human DHRS1 (SDR19C1), a member of the short-chain dehydrogenase/reductase superfamily

  • J Steroid Biochem Mol Biol. 2019 Jan;185:80-89. doi: 10.1016/j.jsbmb.2018.07.013.
Lucie Zemanová 1,  Hana Navrátilová 2,  Rudolf Andrýs 3,  Kristýna Šperková 2,  Jiří Andrejs 2,  Klára Kozáková 2,  Marc Meier 4,  Gabriele Möller 4,  Eva Novotná 2,  Miroslav Šafr 5,  Jerzy Adamski 6,  Vladimír Wsól 2
Affiliations

Affiliations

  • 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. Electronic address: [email protected].
  • 2 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
  • 3 Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic.
  • 4 Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
  • 5 Institute of Legal Medicine, Faculty of Medicine in Hradec Králové, Charles University and University Hospital in Hradec Králové, Sokolská 581, 500 05 Hradec Kralove, Czech Republic.
  • 6 Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Technische Universität München, 85350 Freising-Weihenstephan, Germany; German Center for Diabetes Research (DZD), Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
PMID: 30031147 DOI: 10.1016/j.jsbmb.2018.07.013
Abstract

Many enzymes from the short-chain dehydrogenase/reductase superfamily (SDR) have already been well characterized, particularly those that participate in crucial biochemical reactions in the human body (e.g. 11β-hydroxysteroid dehydrogenase 1, 17β-hydroxysteroid dehydrogenase 1 or carbonyl reductase 1). Several other SDR enzymes are completely or almost completely uncharacterized, such as DHRS1 (also known as SDR19C1). Based on our in silico and experimental approaches, DHRS1 is described as a likely monotopic protein that interacts with the membrane of the endoplasmic reticulum. The highest expression level of DHRS1 protein was observed in human liver and adrenals. The recombinant form of DHRS1 was purified using the detergent n-dodecyl-β-D-maltoside, and DHRS1 was proven to be an NADPH-dependent reductase that is able to catalyse the in vitro reductive conversion of some Steroids (estrone, androstene-3,17-dione and cortisone), as well as other endogenous substances and xenobiotics. The expression pattern and Enzyme activities fit to a role in steroid and/or xenobiotic metabolism; however, more research is needed to fully clarify the exact biological function of DHRS1.

Keywords

DHRS1; SDR superfamily; SDR19C1; Steroid hormones; Xenobiotics.

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