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).
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
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Persson
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Zigler
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Jörnvall
D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D010802:Phylogeny; D011808:Quinone Reductases / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D003459:Crystallins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C063277:VAT-1 protein, Torpedo; D010088:Oxidoreductases; D000426:Alcohol Dehydrogenase; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D011808:Quinone Reductases