Steroids, fatty acyl-CoA, and sterols are substrates of 80-kDa multifunctional protein.
The 2.9-kb mRNA of 17 beta-hydroxysteroid dehydrogenase IV codes for an 80-kDa (737 amino acids) protein featuring domains that are not present in the other human 17 beta-hydroxysteroid dehydrogenases. The N-terminal part reveals conserved motifs of the short-chain alcohol dehydrogenase family. The central- and C-terminal domains are similar to peroxisomal enzymes for beta-oxidation of fatty acids and to sterol carrier protein 2. The 80-kDa protein is N-terminally cleaved to a 32-kDa fragment (amino acids 1-323). Both the 80-kDa and the N-terminal 32-kDa peptides are able to catalyze the dehydrogenation with steroids at the C17 position and 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) facilitates the transfer of 7-dehydrocholesterol and phosphaidylcholine between membranes in vitro. The unique multidomain structure of the 80-kDa protein permits the catalysis of several reactions previously thought to be performed by complexes of different enzymes.
Adamski
J
J
Max-Planck-Institut für experimentelle Endokrinologie, Hannover, Germany.
Leenders
F
F
Carstensen
J F
JF
Kaufmann
M
M
Markus
M M
MM
Husen
B
B
Tesdorpf
J G
JG
Seedorf
U
U
de Launoit
Y
Y
Jakob
F
F
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D003001:Cloning, Molecular; D004746:Enoyl-CoA Hydratase; D005260:Female; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes; D064029:Peroxisomal Multifunctional Protein-2; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D017386:Sequence Homology, Amino Acid; D013256:Steroids / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*; D013347:Subcellular Fractions; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology
D000214:Acyl Coenzyme A; D009097:Multienzyme Complexes; D013256:Steroids; D013261:Sterols; D015067:17-Hydroxysteroid Dehydrogenases; C065185:D-3-hydroxyacyl CoA dehydratase; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase