HSD17B8: Human hydroxysteroid (17-beta) dehydrogenase 8
PDB Code: 2PD6
Type 8 17β-HSD (17β-HSD8) is the product of the Ke6 gene, which has been linked in mice to a recessive form of polycystic kidney disease. The enzyme efficiently inactivates estradiol into estrone and to a lesser extent testosterone into androstenedione in a NAD + dependent manner, as shown with purified protein in vitro and in transfection experiments in intact cells. The protein is highly expressed in liver, kidney and gonadal tissues. Interestingly, the enzyme is expressed in ovaries in cumulus cells, and not in granulosa and luteal cells where the steroidogenic 17β-HSD1 and 17β-HSD7 are expressed indicating a possible role in sex steroid induced development controlled by opposing (inactivation/activation) activities. The gene encodes a protein of 270 amino acids, whose three-dimensional structure has now been determined. Recent modelling studies suggest that 17β-HSD8 might use fatty acyl thioesters as substrates, underlining the close relationships between 17β-HSDs and fatty acid metabolism.
The human gene is located on chromosome 6p21.3, and the enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily.
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