17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus: structural and functional aspects.
17beta-Hydroxysteroid dehydrogenase (17beta-HSD) activity has been described in all filamentous fungi tested, but until now only one 17beta-HSD from Cochliobolus lunatus (17beta-HSDcl) was sequenced. We examined the evolutionary relationship among 17beta-HSDcl, fungal reductases, versicolorin reductase (Ver1), trihydroxynaphthalene reductase (THNR), and other homologous proteins. In the phylogenetic tree 17beta-HSDcl formed a separate branch with Ver1, while THNRs reside in another branch, indicating that 17beta-HSDcl could have similar function as Ver1. The structural relationship was investigated by comparing a model structure of 17beta-HSDcl to several known crystal structures of the short chain dehydrogenase/reductase (SDR) family. A similarity was observed to structures of bacterial 7alpha-HSD and plant tropinone reductase (TR). Additionally, substrate specificity revealed that among the substrates tested the 17beta-HSDcl preferentially catalyzed reductions of steroid substrates with a 3-keto group, Delta(4) or 5alpha, such as: 4-estrene-3,17-dione and 5alpha-androstane-3,17-dione.
Lanisnik Rizner
T
T
Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia. lanisnik@ibmi.mf.uni-lj.si
Stojan
J
J
Adamski
J
J
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001203:Ascomycota / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D013379:Substrate Specificity
D015067:17-Hydroxysteroid Dehydrogenases