title: Evolution of 17beta-HSD type 4, a multifunctional protein of beta-oxidation.
abstract: 17beta-Hydroxysteroid dehydrogenase type 4 (17beta-HSD4) is the most unusual among human 17beta-HSDs. It is characterized by a multidomain structure, in which the dehydrogenase domain is fused to a hydratase and a lipid transfer domain. 17beta-HSD4 not only inactivates estradiol by conversion to estrone but its three protein domains also participate in successive steps of peroxisomal beta-oxidation of long- and branched-chain fatty acids. We have compared the genomic structure of human 17beta-HSD4 and several homologous genes from lower animals and fungi. Our data suggest an evolutionary scenario for the three protein domains and indicate a highly dynamic history of the enzyme but also a very high conservation of multifunctionality. This suggests that the main function of human 17beta-HSD4 is still its involvement in fatty-acid metabolism, while steroid conversion is only a secondary and possibly minor activity in vivo.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute for Experimental Genetics, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Breitling
authors.forename: Z
authors.initials: Z
authors.lastname: Marijanović
authors.forename: D
authors.initials: D
authors.lastname: Perović
authors.forename: J
authors.initials: J
authors.lastname: Adamski
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000201:enzymology; D002176:Candida albicans / Q000201:enzymology; D004331:Drosophila melanogaster / Q000201:enzymology; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D019143:Evolution, Molecular; D005227:Fatty Acids / Q000378:metabolism; D005658:Fungi / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D009492:Neurospora crassa / Q000201:enzymology; D010084:Oxidation-Reduction; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D005227:Fatty Acids; D007527:Isoenzymes; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases