The gamma1 and gamma2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties

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Abstract
CDNA clones corresponding to two alleles of the ADH3 locus were identified by hybridization with synthetic oligodeoxyribonucleotides specific for class I human liver alcohol dehydrogenase. Sequences were determined for a 1457-nucleotide cDNA, covering the whole .gamma.2-coding region, and a 1224-nucleotide cDNA, including the region coding for amino acid residues 53-374 of the .gamma.1 subunit. Two amino acid replacements between the .gamma.1 and .gamma.2 subunits were identified. At position 349, isoleucine in .gamma.1 instead of valine in .gamma.2 is a conservative exchange of a superficial residue which has been ascribed no special importance. The other exchange, at position 271, arginine in .gamma.1 and glutamine in .gamma.2, explains differences in enzyme properties. Electrophoretically, it is consistent with the less cathodic mobility of the .gamma.2 subunit. Functionally, the location of the exchange at the surface of the coenzyme-binding pocket may influence the dissociation of the reduced coenzyme.