17 beta-hydroxysteroid dehydrogenase type 7 - an ancient 3-ketosteroid reductase of cholesterogenesis

17 beta -hydroxysterold dehydrogenase type 7 (17 beta -HSD7) is a novel est rogenic hydroxysteroid dehydrogenase from mammals. We modeled the three-dim ensional structure of human 17 beta -HSD7, analyzed the phylogeny of 17 bet a -HSD7 homologues and determined its expression pattern by in silico North ern blotting. Predominant expression is found not only in reproductive tiss ues (breast, ovary, placenta) but also in liver and developing brain, princ ipal sites of cholesterol synthesis. The substrate binding pocket is openin g towards a conserved membrane-associated helix, which is indicative for a conversion of a membrane component. 17 beta -HSD7 shows significant homolog y to a yeast 3-ketosteroid reductase (ERG27) involved in ergosterol biosynt hesis. Our results lead to the conclusion that 17 beta -HSD7 is not only in volved in estradiol production but plays another land possibly more importa nt) role as a 3-ketosteroid reductase in cholesterogenesis. This agrees wit h the striking absence of 17 beta -HSD7 homologues in the complete genomes of Drosophila and C. elegans which are both auxotrophic for cholesterol. (C ) 2001 Elsevier Science Ireland Ltd. All rights reserved.