Abstract
The family of short-chain dehydrogenases/reductases (SDR) with subunits of typically 250-odd amino acid residues now encompasses 57 different characterised proteins, representing a wide variety of enzyme activities. The first characterised member of this family was the fruit-fly alcohol dehydrogenase (Schwartz and Jörnvall, 1976; Thatcher, 1980). This alcohol dehydrogenase is different from the classical liver alcohol dehydrogenase, which has larger subunits of about 370 residues, is zinc-dependent, and belongs to a family of medium-chain dehydrogenases/reductases (MDR) (Jörnvall et al., 1981; Persson et al., 1994). In the early 80’s, two additional structures were shown to be related to the Drosophila alcohol dehydrogenase (Jörnvall et al., 1981, 1984), thus establishing a new enzyme family. These structures were glucose dehydrogenase (Jany et al., 1984) and ribitol dehydrogenase (Morris et al., 1974; Dothie et al., 1985). Already at this stage, it was seen that the molecular architecture was different between this short-chain dehydrogenase family and the medium-chain dehydrogenases. The coenzyme-binding region is located at the beginning of the C-terminal domain in the medium-chain dehydrogenases, with a classical Rossmann fold (Rossmann et al., 1975) and a conserved Gly-X-Gly-X-X-Gly pattern. In contrast, the short-chain dehydrogenases have a similar pattern of Gly-X-Gly-X-X-X-Gly at the N-terminal region. In addition, secondary structure predictions suggested this region to have a β-turn-α-turn-β motif, compatible with a Rossmann fold (Thatcher & Sawyer, 1980). Consequently, it was early clear that the two different families of dehydrogenases have different molecular architectures. The medium-chain dehydrogenases have an N-terminal, catalytic domain and a C-terminal, coenzyme-binding domain, while in the shortchain dehydrogenases the coenzyme-binding is located N-terminally and the catalytic site toward the C-terminal half of the molecule (Jörnvall et al., 1981).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Albalat, R., Gonzàlez-Duarte, R., and Atrian, S., 1992, Protein engineering of Drosophila alcohol dehydrogenase. Thy hydroxyl group of Tyr152 is involved in the active site of the enzyme, FEBS Lett. 308:235–239.
Aziz, N., Maxwell, M. M., St.-Jacques, B., and Brenner, B. M., 1993, Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease, Mol. Cell. Biol. 13:1847–1853.
Bairoch, A., and Boeckmann, B., 1992, The SWISS-PROT protein sequence data bank, Nucleic Acids Res. 20 Supplement:2019–2022.
Baron, S. F., Franklund, C. V., and Hylemon, P. B., 1991, submitted to the EMBL databank.
Bauer, A. J., Rayment, I., Frey, P. A., and Holden, H. M., 1992, The molecular structure of UDP-galactose 4-epimerase from Escherichia coli determined at 2.5 Å resolution, Proteins 12:372–381.
Bauer, S., Galliano, H., Pfeiffer, F., Meßner, B., Sandermann, Jr, H., and Ernst, D., 1993, Isolation and characterization of a cDNA clone encoding a novel short-chain alcohol dehydrogenase from norway spruce (Picea abies L. Karst), Plant Physiol. 103:1479–1480.
Callahan, H. L., and Beverley, S. M., 1992, A member of the aldoketo reductase family confers methotrexate resistance in Leishmania, J. Biol. Chem. 267:24165–24168.
Chen, Z., Jiang, J. C., Lin, Z.-G., Lee, W. R., Baker, M. E., and Chang, S. H., 1993, Site specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis, Biochemistry 32:3342–3346.
DeLong, A., Calderon-Urrea, A., and Dellaporta, S. L. (1993) Sex determination gene TASSELSEED2 of maize encodes a short-chain alcohol dehydrogenase required for stage-specific floral organ abortion, Cell 74:757–768.
Dothie, J. M., Giglio, J. R., Moore, C. B., Taylor, S. S., and Hartley, B. S., 1985, Ribitol dehydrogenase of Klebsiella aerogenes. Sequence and properties of wild-type and mutant strains, Biochem. J. 230:569–578.
Ensor, C. M., and Tai, H.-H., 1991, Site-directed mutagenesis of the conserved tyrosine 151 of human placental NAD+-dependent 15-hydroxyprostaglandin dehydrogenase yields a catalytically inactive enzyme, Biochem. Biophys. Res. Commun. 176:840–845.
Geissler, W. M., Davis, D. L., Wu, L., Bradshaw, K. D., Patel, S., Mendonca, B. B., Elliston, K. O., Wilson, J. D., Russell, D. W., and Andersson, S. (1994) Male pseudohermaphroditism caused by mutations of testicular 17β-hydroxysteroid dehydrogenase 3, Nature Genetics 7:34–39.
Ghosh, D., Weeks, C. M., Grochulski, P., Duax, W L., Erman, M., Rimsay, R. L., and Orr, J. C., 1991, Three-dimensional structure of holo 3α,20β-hydroxysteroid dehydrogenase: A member of a shortchain dehydrogenase family, Proc. Natl Acad. Sci. 88:10064–10068.
Holm, L., Sander, C., and Murzin, A., 1994, Three sisters, different names, Nature Structural Biology 1:146–147.
Horinouchi, S., Ishizuka, H., and Beppu, T., 1991, Cloning, nucleotide sequence and transcriptional analysis of the NAD(P)-dependent cholesterol dehydrogenase gene from a Nocardia sp. and its hyperexpression in Streptomyces sp., Appl. Environ. Microbiol. 57:1386–1393.
Ichinose, H., Katoh, S., Sueoka, T., Titani, K., Fujita, K., and Nagatsu, T., 1991, Cloning and sequencing of cDNA encoding human sepiapterin reductase, Biochem. Biophys. Res. Commun. 179:183–189.
Krook, M., Marekov, L., and Jörnvall, H., 1990, Purification and structural characterization of placental NAD+-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family, Biochemistry 29:738–743.
Jany, K.-D., Ulmer, W., Fröschle, M., and Pfleiderer, G., 1984, Complete amino acid sequence of glucose dehydrogenase from Bacillus megaterium, FEBS Lett. 165:6–10.
Jörnvall, H., Persson, M., and Jeffery, J., 1981, Alcohol and polyol dehydrogenases are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type, Proc. Natl Acad. Sci. USA 78:4226–4230.
Jörnvall, H., von Bahr-Lindström, H., Jany, K.-D., Ulmer, W., and Fröschle, M., 1984, Extended superfamily of short alcohol-polyol-sugar dehydrogenases: Structural similarities between glucose and ribitol dehydrogenases, FEBS Lett. 165:190–196.
Kimura, M., 1983, The neutral theory of molecular evolution. Cambridge University Press, Cambridge, England.
Krook, M., Prozorovski, V., Atrian, S., Gonzàlez-Duarte, R., and Jörnvall, H., 1992, Short-chain dehydrogenases. Proteolysis and chemical modification of prokaryotic 3α/20β-hydroxysteroid, insect alcohol and human 15-hydroxyprostaglandin dehydrogenases, Eur. J. Biochem. 209:233–239.
Marekov, L., Krook, M., and Jörnvall, H., 1990, Prokaryotic 20β-hydroxysteroid dehydrogenase is an enzyme of the’ short-chain, non-metalloenzyme’ alcohol dehydrogenase type, FEBS Lett. 266:51–54.
McKinley-McKee, J. S., Winberg, J.-O., and Pettersson, G., 1991, Mechanism of action of Drosophila melanogaster alcohol dehydrogenase, Biochem. Internat. 25:879–885.
Morris, H. R., Williams, D. H., Midwinter, G. G., and Hartley, B. S., 1974, A mass-spectrometric sequence study of the enzyme ribitol dehydrogenase from Klebsiella aerogenes, Biochem. J. 141:701–713.
Nakajima, K., Hashimoto, T., and Yamada Y., 1993, Two tropinone reductases with different stereospecificities are short-chain dehydrogenases evolved from a common ancestor, Proc. Natl Acad. Sci. U.S.A. 90:9591–9595.
Peltoketo, H., Isomaa, V., Mäentausta, O., and Vihko, R., 1988, Complete amino acid sequence of human placental 17β-hydroxysteroid dehydrogenase deduced from cDNA, FEBS Lett. 239:73–77.
Persson, B., Krook, M., and Jörnvall, H., 1991, Characteristics of short-chain alcohol dehydrogenases and related enzymes, Eur. J. Biochem. 200:537–543.
Persson, B., Zigler, Jr, J. S., and Jörnvall, H., 1994, A super-family of medium-chain dehydrogenases/reductases (MDR): Sub-lines including ζ-crystallin, alcohol and polyol dehydrogenases, quinone oxidore-ductases, enoyl reductases, VAT-1 and further proteins, Eur. J. Biochem., submitted.
Rat, L., Veuille, M., and Lepesant, J. A., 1991, Drosophila fat body protein P6 and alcohol dehydrogenase are derived from a common ancestral protein, J. Mol. Evol. 33:194–203.
Rossmann, M. G., Liljas, A., Brändén, C.-I., and Banaszak, L. J., 1975, Evolutionary and structural relationships among dehydrogenases, The Enzymes, 3rd edn (Boyer, P. D., ed.), vol. 11, pp. 61–102, Academic Press, New York.
Saitou, N., and Nei, M., 1987, The neighbor-joining method: A new method for reconstructing phylogenetic trees, Mol. Biol. Evol. 4:406–425.
Schwartz, M. F., and Jörnvall, H., 1976, Structural analyses of mutant and wild-type alcohol dehydrogenses from Drosophila melanogaster, Eur. J. Biochem. 68:159–168.
Skory, C. D., Chang, P. K., Cary, J., and Linz, J. E., 1992, Isolation and characterization of a gene from Aspergillus parasiticus associated with the conversion of versicolorin A to sterigmatocystin in aflatoxin biosynthesis, Appl. Environ. Microbiol. 58:3527–3537.
Suzuki, K., Ueda, S., Sugiyama, M., and Imamura, S., 1993, Cloning and expression of a Pseudomonas 3α-hydroxysteroid dehydrogenase-encoding gene in Escherichia coli, Gene 130:137–140.
Thatcher, D. R., 1980, The complete amino acid sequence of three alcohol dehydrogenase alleloenzymes (Adh N-11, Adh s and Adh UF) from the fruitfly Drosophila melanogaster, Biochem. J. 187:875–883.
Thatcher, D. R., and Sawyer, L., 1980, Secondary structure prediction from the sequence of Drosophila melanogaster (fruitfly) alcohol dehydrogenase, Biochem. J. 187:884–886.
Thompson, J. D., Higgins, D. G., and Gibson, T. J., 1994, Improved sensitivity of profile searches through the use of sequence weights and gap excision, Comput. Appl. Biosci. 10:19–29.
Varughese, K. I., Skinner, M. M., Whiteley, J. M., Matthews, D. A., and Xuong, N. H., 1992, Crystal structure of rat liver dihydropteridine reductase, Proc. Natl Acad. Sci. USA 89:6080–6084.
Wong, B., 1993, submitted to the EMBL/GenBank/DDBJ databases.
Wu, L., Einstein, M., Geissler, W. M., Chan, H. K., Elliston, K. O., and Andersson, S. (1993) Expression cloning and characterization of a human 17β-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20α-hydroxysteroid dehydrogenase activity, J. Biol. Chem. 268:12964–12969.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Persson, B., Krook, M., Jörnvall, H. (1995). Short-Chain Dehydrogenases/Reductases. In: Weiner, H., Holmes, R.S., Wermuth, B. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 5. Advances in Experimental Medicine and Biology, vol 372. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1965-2_46
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1965-2_46
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5808-4
Online ISBN: 978-1-4615-1965-2
eBook Packages: Springer Book Archive