The γ1 and γ2 subunits of human liver alcohol dehydrogenase: cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties

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 γ2‐coding region, and a 1224‐nucleotide cDNA, including the region coding for amino acid residues 53–374 of the γ1 subunit. Two amino acid replacements between the γ1 and γ2 subunits were identified. At position 349, isoleucine in γ1 instead of valine in γ2 is a conservative exchange of a superficial residue which has been ascribed no special importance. The other exchange, at position 271, arginine in γ1 and glutamine in γ2, explains differences in enzyme properties. Electrophoretically, it is consistent with the less cathodic mobility of the γ2 subunit. Functionally, the location of the exchange at the surface of the coenzyme‐binding pocket may influence the dissociation of the reduced coenzyme. Copyright © 1986, Wiley Blackwell. All rights reserved