Evolution of 17 beta-HSD type 4, a multifunctional protein of beta-oxidation

17 beta -Hydroxysteroid dehydrogenase type 1 (17 beta -HSD4) is the most un usual among human 17 beta -HSDs. It is characterized by a multidomain struc ture, in which the dehydrogenase domain is fused to a hydratase and a lipid transfer domain. 17 beta -HSD4 not only inactivates estradiol by conversio n to estrone but its three protein domains also participate in successive s teps of peroxisomal beta -oxidation of long- and branched-chain fatty acids . We have compared the genomic structure of human 17 beta -HSD4 and several homologous genes from lower animals and fungi. Our data suggest an evoluti onary scenario for the three protein domains and indicate a highly dynamic history of the enzyme but also a very high conservation of multifunctionali ty. This suggests that the main function of human 17 beta -HSD4 is still it s involvement in fatty-acid metabolism while steroid conversion is only a s econdary and possibly minor activity in vivo. (C) 2001 Elsevier Science Ire land Ltd. All rights reserved.