cDNA and protein structure for the alpha subunit of human liver alcohol dehydrogenase.
Two cDNA clones for human liver alcohol dehydrogenase (ADH) were identified, together covering 1450 nucleotides that contain the cDNA sequence of the ADH1 locus and include a coding region of 1122 nucleotides for the alpha subunit of the enzyme. In parallel, direct peptide analyses of the carboxymethylated protein also established most of the amino acid sequence. Nucleotide and peptide data were in complete agreement and show exchanges at 24 positions in the alpha relative to the beta subunit. One of the cDNA clones had a 139-nucleotide internal deletion at a position of possible interest in relation to mRNA processing, ancestral connections, or DNA replication. The structure of the alpha subunit is homologous to that of the beta and gamma subunits but has many exchanges, also of functionally important residues, explaining the different enzymatic properties. In total, 35 of 374 amino acid residues differ between the class I isozymes, and the substitutions add an extra SH group in the alpha subunit. Only in the beta-pleated sheet region of the coenzyme-binding domain is almost complete lack of substitutions noted, illustrating the importance of this region. In contrast, the active site region is far less conserved. However, similar exchanges of functional significance have also been found in distantly related alcohol and polyol dehydrogenases.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis*; D004262:DNA Restriction Enzymes; D006801:Humans; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D009693:Nucleic Acid Hybridization; D010957:Plasmids
D046911:Macromolecular Substances; D004247:DNA; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D004262:DNA Restriction Enzymes