A super-family of medium-chain dehydrogenases/reductases (MDR). Sub-lines including zeta-crystallin, alcohol and polyol dehydrogenases, quinone oxidoreductase enoyl reductases, VAT-1 and other proteins.

The protein super-family of medium-chain alcohol dehydrogenases (and glutathione-dependent formaldehyde dehydrogenase), polyol dehydrogenases, threonine dehydrogenase, archaeon glucose dehydrogenase, and eye lens reductase-active zeta-crystallins also includes Escherichia coli quinone oxidoreductase, Torpedo VAT-1 protein, and enoyl reductases of mammalian fatty acid and yeast erythronolide synthases. In addition, two proteins with hitherto unknown function are shown to belong to this super-family of medium-chain dehydrogenases and reductases (MDR). Alignment of zeta-crystallins/quinone oxidoreductases/VAT-1 reveals 38 strictly conserved residues, of which approximately half are glycine residues, including those at several space-restricted turn positions and critical coenzyme-binding positions in the alcohol dehydrogenases. This indicates a conserved three-dimensional structure at the corresponding parts of these distantly related proteins and a conserved binding of a coenzyme in the two proteins with hitherto unknown function, thus ascribing a likely oxidoreductase function to these proteins. When all forms are aligned, including enoyl reductases, a zeta-crystallin homologue from Leishmania and the two proteins with hitherto unknown function, only three residues are strictly conserved among the 106 proteins characterised within the superfamily, and significantly these residues are all glycines, corresponding to Gly66, Gly86 and Gly201 of mammalian class I alcohol dehydrogenase. Notably, these residues are located in different domains. Hence, a distant origin and divergent functions, but related forms and interactions, appear to apply to the entire chains of the many prokaryotic and eukaryotic members. Additionally, in the zeta-crystallins/quinone oxidoreductases, a highly conserved tyrosine residue is found. This residue, in the three-dimensional structure of the homologous alcohol dehydrogenase, is positioned at the subunit cleft that contains the active site and could therefore be involved in catalysis. If so, this residue and its role may resemble the pattern of a conserved tyrosine residue in the different family of short-chain dehydrogenases/reductases (SDR).

[1]  H. Jörnvall,et al.  Features of structural zinc in mammalian alcohol dehydrogenase. Site-directed mutagenesis of the zinc ligands. , 1994, European journal of biochemistry.

[2]  J. Pawlowski,et al.  Overexpression and mutagenesis of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Role of cysteines and tyrosines in catalysis. , 1994, The Journal of biological chemistry.

[3]  Julie Dawn Thompson,et al.  Improved sensitivity of profile searches through the use of sequence weights and gap excision , 1994, Comput. Appl. Biosci..

[4]  M. Linial.  VAT-1 from Torpedo electric organ forms a high-molecular-mass protein complex within the synaptic vesicle membrane. , 1993, European journal of biochemistry.

[5]  B. Persson,et al.  ζ‐Crystallin versus other members of the alcohol dehydrogenase super‐family Variability as a functional characteristic , 1993, FEBS letters.

[6]  M. Baker,et al.  Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis. , 1993, Biochemistry.

[7]  M. Linial,et al.  The protein VAT-1 from Torpedo electric organ exhibits an ATPase activity , 1993, Neuroscience Letters.

[8]  H. Jörnvall,et al.  Comparative proteolysis of sorbitol and alcohol dehydrogenases. , 1993, European journal of biochemistry.

[9]  J. Zigler,et al.  Molecular cloning and sequencing of zeta-crystallin/quinone reductase cDNA from human liver. , 1993, Biochemical and biophysical research communications.

[10]  D. Hough,et al.  Cloning, sequencing and expression of the gene encoding glucose dehydrogenase from the thermophilic archaeon Thermoplasma acidophilum. , 1993, European journal of biochemistry.

[11]  M. Linial,et al.  VAT‐1 from Torpedo is a membranous homologue of zeta crystallin , 1993, FEBS letters.

[12]  Roser Gonzàlez-Duarte,et al.  Short-chain dehydrogenases , 1992 .

[13]  I. Rodriguez,et al.  A guinea-pig hereditary cataract contains a splice-site deletion in a crystallin gene. , 1992, Biochimica et biophysica acta.

[14]  S. Atrian,et al.  Protein engineering of Drosophila alcohol dehydrogenase The hydroxyl group of Tyr152 is involved in the active site of the enzyme , 1992, FEBS letters.

[15]  H. Jörnvall,et al.  A synthetic peptide encompassing the binding site of the second zinc atom (the 'structural' zinc) of alcohol dehydrogenase. , 1992, European journal of biochemistry.

[16]  J. Cronan,et al.  The gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase. , 1992, The Journal of biological chemistry.

[17]  J. Zigler,et al.  Identification and characterization of the enzymatic activity of zeta-crystallin from guinea pig lens. A novel NADPH:quinone oxidoreductase. , 1992, The Journal of biological chemistry.

[18]  A. Bairoch,et al.  The SWISS-PROT protein sequence data bank. , 1991, Nucleic acids research.

[19]  M Krook,et al.  Characteristics of short-chain alcohol dehydrogenases and related enzymes. , 1991, European journal of biochemistry.

[20]  J B McAlpine,et al.  Modular organization of genes required for complex polyketide biosynthesis. , 1991, Science.

[21]  H. Tai,et al.  Site-directed mutagenesis of the conserved tyrosine 151 of human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase yields a catalytically inactive enzyme. , 1991, Biochemical and biophysical research communications.

[22]  A. Bairoch.  PROSITE: a dictionary of sites and patterns in proteins. , 1991, Nucleic acids research.

[23]  D. Garland,et al.  zeta-Crystallin is a major protein in the lens of Camelus dromedarius. , 1991, Archives of biochemistry and biophysics.

[24]  J. Zigler,et al.  Zeta-crystallin from guinea pig lens is capable of functioning catalytically as an oxidoreductase. , 1991, Archives of biochemistry and biophysics.

[25]  H. Jörnvall,et al.  The transcripts of zeta-crystallin, a lens protein related to the alcohol dehydrogenase family, are altered in a guinea-pig hereditary cataract. , 1990, Experimental eye research.

[26]  Manuel B. Datiles III,et al.  Association of hereditary cataracts in strain guinea-pigs with mutation of the gene for ζ-crystallin , 1990 .

[27]  H. Jörnvall,et al.  Variability within mammalian sorbitol dehydrogenases. The primary structure of the human liver enzyme. , 1989, European journal of biochemistry.

[28]  B. Persson,et al.  Eye lens zeta-crystallin relationships to the family of "long-chain" alcohol/polyol dehydrogenases. Protein trimming and conservation of stable parts. , 1989, Biochemistry.

[29]  T. Borrás,et al.  Zeta-crystallin, a novel protein from the guinea pig lens is related to alcohol dehydrogenases. , 1989, Gene.

[30]  J. Naggert,et al.  Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[31]  B. Aronson,et al.  The primary structure of Escherichia coli L-threonine dehydrogenase. , 1989, The Journal of biological chemistry.

[32]  M. Linial,et al.  VAT 1: An abundant membrane protein from torpedo cholinergic synaptic vesicles , 1989, Neuron.

[33]  H. Jörnvall,et al.  Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes. , 1988, Biochemistry.

[34]  B. Persson,et al.  Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases. , 1987, European journal of biochemistry.

[35]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[36]  J. Piatigorsky,et al.  Recruitment of enzymes as lens structural proteins. , 1987, Science.

[37]  J. Zigler,et al.  Zeta-crystallin, a novel lens protein from the guinea pig. , 1987, Current eye research.

[38]  W. W. Jong,et al.  The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses , 1987, Nature.

[39]  H. Jörnvall,et al.  The gamma 1 and gamma 2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties. , 1986, European journal of biochemistry.

[40]  P Argos,et al.  A conformational preference parameter to predict helices in integral membrane proteins. , 1986, Biochimica et biophysica acta.

[41]  H. Eklund,et al.  Molecular aspects of functional differences between alcohol and sorbitol dehydrogenases. , 1985, Biochemistry.

[42]  M. Kimura.  The Neutral Theory of Molecular Evolution: Introduction , 1983 .

[43]  D. Russell,et al.  Nucleotide sequence of the yeast alcohol dehydrogenase II gene. , 1983, The Journal of biological chemistry.

[44]  H. Jörnvall,et al.  The primary structure of yeast alcohol dehydrogenase. , 1977, European journal of biochemistry.

[45]  H. Eklund,et al.  Three-dimensional structure of horse liver alcohol dehydrogenase at 2-4 A resolution. , 1976, Journal of molecular biology.

[46]  H. Eklund,et al.  3 Alcohol Dehydrogenases , 1975 .

[47]  Anders Liljas,et al.  2 Evolutionary and Structural Relationships among Dehydrogenases , 1975 .

[48]  L. H. Jensen.  X-ray structural studies of ferredoxin and related electron carriers. , 1974, Annual review of biochemistry.

[49]  B. Vallee,et al.  Considerations in evaluating the zinc content of horse liver alcohol dehydrogenase preparations. , 1969, Biochemistry.