Steroids, fatty acyl-CoA, and sterols are substrates of 80-kDa multifunctional protein

Abstract

The 2.9-kb mRNA of 17β-hydroxysteroid dehydrogenase IV codes for an 80-kDa (737 amino acids) protein featuring domains that are not present in the other human 17β-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 β-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 5977ndash;737) facilitates the transfer of 7-dehydrocholesterol and phosphatidylcholine 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.