Porcine 80-kDa protein reveals intrinsic 17 beta-hydroxysteroid dehydrogenase, fatty acyl-CoA-hydratase/dehydrogenase, and sterol transfer activities.
Four types of 17beta-hydroxysteroid dehydrogenases have been identified so far. The porcine peroxisomal 17beta-hydroxysteroid dehydrogenase type IV catalyzes the oxidation of estradiol with high preference over the reduction of estrone. A 2.9-kilobase mRNA codes for an 80-kDa (737 amino acids) protein featuring domains which are not present in the other 17beta-hydroxysteroid dehydrogenases. The 80-kDa protein is N terminally cleaved to a 32-kDa fragment with 17beta-hydroxysteroid dehydrogenase activity. Here we show for the first time that both the 80-kDa and the N-terminal 32 kDa (amino acids 1-323) peptides are able to perform the dehydrogenase reaction not only with steroids at the C17 position but also with 3-hydroxyacyl-CoA. The central part of the 80-kDa protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-CoA hydratase reaction with high efficiency. The C-terminal part of the 80-kDa protein (amino acids 597-737) is similar to sterol carrier protein 2 and facilitates the transfer of 7-dehydrocholesterol and phosphatidylcholine between membranes in vitro. The unique multidomain structure of the 80-kDa protein allows for the catalysis of several reactions so far thought to be performed by complexes of different enzymes.
Leenders
F
F
Max-Planck-Institut für experimentelle Endokrinologie, 30603 Hannover, Germany.
Tesdorpf
J G
JG
Markus
M
M
Engel
T
T
Seedorf
U
U
Adamski
J
J
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000378:metabolism*; D042964:Acyl-CoA Dehydrogenase; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D004746:Enoyl-CoA Hydratase / Q000096:biosynthesis / Q000378:metabolism*; D004926:Escherichia coli; D044943:Fatty Acid Desaturases / Q000096:biosynthesis / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007668:Kidney; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018996:Myelin P2 Protein / Q000096:biosynthesis / Q000378:metabolism*; D009363:Neoplasm Proteins; D010713:Phosphatidylcholines / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013552:Swine; D014162:Transfection; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D017931:DNA Primers; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D010713:Phosphatidylcholines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D015067:17-Hydroxysteroid Dehydrogenases; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D004746:Enoyl-CoA Hydratase