17 beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus:structural and functional aspects

17 beta -Hydroxysteroid debydrogenase (17 beta -HSD) activity has been desc ribed in all filamentous fungi tested, but until now only one 17 beta -HSD from Cochliobolus lunatus (17 beta -HSDcl) was sequenced. We examined the e volutionary relationship among 17 beta -HSDcl, fungal reductases, versicolo rin reductase (Ver1), trihydroxynaphthalene reductase (THNR), and other hom ologous proteins. In the phylogenetic tree 17 beta -HSDcl formed a separate branch with Veri, while THNRs reside in another branch, indicating that 17 beta -HSDcl could have similar function as Veri. The structural relationsh ip was investigated by comparing a model structure of 17P-HSDcl to several known crystal structures of the short chain dehydrogenase/reductase (SDR) f amily. A similarity was observed to structures of bacterial 7 alpha -HSD an d plant tropinone reductase (TR). Additionally, substrate specificity revea led that among the substrates tested the 17 beta -HSDcl preferentially cata lyzed reductions of steroid substrates with a 3-keto group, Delta (4) or 5 alpha such as: 4-estrene-3,17-dione and 5 alpha -androstane-3,17-dione. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.