[Structure and function of peroxisomal tetrameric carbonyl reductase].
In this paper, the structure and function of a new tetrameric carbonyl reductase (TCR) is reviewed. TCRs were purified from rabbit and pig heart, using 4-benzoylpyridine as a substrate. Partial peptide sequencing and cDNA cloning of rabbit and pig TCRs revealed that both enzymes belonged to the short-chain dehydrogenase/reductase family and that their subunits consisted of 260 amino acid residues. Rabbit and pig TCRs catalyzed the reduction of alkyl phenyl ketones, alpha-dicarbonyl compounds, quinones and retinals. Both enzymes were potently inhibited by flavonoids and fatty acids. 9,10-Phenanthrenequinone, which is efficiently reduced by rabbit and pig TCRs, mediated the formation of superoxide radical through its redox cycling in pig heart. The C-terminal sequences of rabbit and pig TCRs comprised a type 1 peroxisomal targeting signal (PTS1) Ser-Arg-Leu, suggesting that the enzymes are localized in the peroxisome. In fact, pig TCR was targeted into the peroxisomal matrix, in the case of transfection of HeLa cells with vectors expressing the enzyme. However, when the recombinant pig TCR was directly introduced into HeLa cells, the enzyme was not targeted into the peroxisomal matrix. The crystal structure of recombinant pig TCR demonstrated that the C-terminal PTS1 of each subunit of the enzyme was buried in the interior of the tetrameric molecule. These findings indicate that pig TCR is imported into the peroxisome as a monomer and then forms an active tetramer within this organelle.
Imamura
Yorishige
Y
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan. yorishig@gpo.kumamoto-u.ac.jp
D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D003461:Crystallography; D006801:Humans; D020675:Peroxisomes / Q000201:enzymology*; D021381:Protein Transport; D011817:Rabbits; D013379:Substrate Specificity; D013552:Swine; D014018:Tissue Distribution
D000429:Alcohol Oxidoreductases