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Dehydrogenase/reductase (SDR family) member 7 (DHRS7, retSDR4, SDR34C1) is a previously uncharacterized member of the short-chain dehydrogenase/reductase (SDR) superfamily. While human SDR members are known to play an important role in various (patho)biochemical pathways including intermediary metabolism and biotransformation of xenobiotics, only 20% of them are considered to be well characterized. Based on phylogenetic tree and SDR sequence clusters analysis DHRS7 is a close relative to well-known SDR member 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) that participates in metabolism of endogenous and xenobiotic substances with carbonyl group. The aim of present study is to determine the basic biochemical properties of DHRS7 and its possible involvement in metabolism of substrates with carbonyl group. For the first time the computational predictions of this membrane protein and membrane topology were experimentally confirmed. DHRS7 has been demonstrated to be an integral protein facing the lumen of the endoplasmic reticulum with lack of posttranscriptional glycosylation modification. Subsequently, NADP(H) cofactor preference and enzymatic reducing activity of DHRS7 was determined towards endogenous substrates with a steroid structure (cortisone, 4-androstene-3,17-dion) and also toward relevant exogenous substances bearing a carbonyl group harmful to human health (1,2-naphtoquinone, 9,10-phenantrenequinone). In addition to 11β-HSD1, DHRS7 is another enzyme from SDR superfamily that have been proved, at least in vitro, to contribute to the metabolism of xenobiotics with carbonyl group.

Original publication

DOI

10.1016/j.cbi.2013.11.003

Type

Journal article

Journal

Chem Biol Interact

Publication Date

25/01/2014

Volume

207

Pages

52 - 57

Keywords

11β-HSD1, 11β-hydroxysteroid dehydrogenase, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, DHRS7, ER, Membrane topology, NNAL, NNK, Oxidoreductase activity, SDR, SDR34C1, Short-chain dehydrogenases/reductases, dehydrogenase/reductase (SDR family) member 7, endoplasmic reticulum, short-chain dehydrogenases/reductases, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Amino Acid Sequence, Animals, Benzaldehydes, Blotting, Western, Fluorescent Antibody Technique, Humans, Intracellular Membranes, Isoenzymes, Kinetics, Microsomes, Liver, Molecular Sequence Data, NAD, NADP, Nitrosamines, Oxidoreductases, Sf9 Cells, Spectrophotometry, Substrate Specificity, Ultracentrifugation